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Qian S, He Y, Li R, Sun P, Zhang X, Pan L, Xu Z, Feng Z, Lian R, Yu L. Polymeric immunoglobulin receptor (pIgR) in cancer progression: a critical role and potential therapeutic target. Apoptosis 2025:10.1007/s10495-025-02116-x. [PMID: 40415061 DOI: 10.1007/s10495-025-02116-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/07/2025] [Indexed: 05/27/2025]
Abstract
Polymeric immunoglobulin receptor (pIgR) is a crucial receptor that primarily mediates the transcytosis of immunoglobulins A and M across epithelial cells, emerging as an essential participant in modulating both mucosal immunity and innate immunity. Recently, pIgR dysregulation in cancer has garnered widespread attention. It exhibits distinct mechanisms and effects across various cancer types with significant clinical value as a biomarker for malignant tumor diagnosis and prognosis evaluation. Recent therapeutic advances have revealed promising strategies, including dimeric IgA-based approaches targeting intracellular oncogenic drivers through pIgR-mediated transcytosis, small molecule modulators such as bufalin, and targeting EV-pIgR with neutralizing antibodies. Integrating these approaches with conventional therapies presents opportunities for enhanced treatment efficacy. Specifically, blocking EV-pIgR with neutralizing antibodies, when integrated with conventional hepatocellular carcinoma therapies such as sorafenib or other therapeutic agents, or a dIgA-targeting approach combined with immune checkpoint inhibitors, may enhance treatment efficacy. This review also addresses current challenges and future directions in pIgR-targeted cancer therapy, emphasizing the need for a deeper understanding of pIgR's regulatory mechanisms. These insights reveal that pIgR is an emerging therapeutic target with significant potential for the development of novel cancer treatment strategies.
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Affiliation(s)
- Shaoju Qian
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
- Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan, 453003, China
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, People's Republic of China
| | - Yeqing He
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
| | - Ruixue Li
- Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, People's Republic of China
| | - Panpan Sun
- Department of Pathology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, People's Republic of China
| | - Xingyi Zhang
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
| | - Lin Pan
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
| | - Zhishan Xu
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
- Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan, 453003, China
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, People's Republic of China
| | - Zhiwei Feng
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China
- Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan, 453003, China
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, People's Republic of China
| | - Rong Lian
- Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, People's Republic of China.
| | - Lili Yu
- School of Basic Medical Sciences, Xinxiang Medical University, #601 Jinsui Road, Xinxiang, 453003, Henan, People's Republic of China.
- Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan, 453003, China.
- Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, People's Republic of China.
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Zhang S, Zhao H, Wang K, Li L, Pan Q, Lu M, Zhang X. Tracing the history of clinical practice of liquid biopsy: a bibliometric analysis. Front Immunol 2025; 16:1574736. [PMID: 40433362 PMCID: PMC12105997 DOI: 10.3389/fimmu.2025.1574736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 04/23/2025] [Indexed: 05/29/2025] Open
Abstract
Introduction Liquid biopsy holds great promise in clinical diagnosis, treatment, and prognostic monitoring. This study reveals the development of liquid biopsy in clinical practice through a comprehensive bibliometric analysis. Methods A total of 40 years of research literature in this field was included from the Web of Science Core Collection (WoSCC), analyzing the evolving research trends of liquid biopsy in clinical practice. We constructed co-occurrence networks for countries, institutions, authors, and keywords, integrating citation analysis and journal impact metrics to provide a comprehensive view of the research landscape in the field of liquid biopsy. Results The results show a significant growth trend in the clinical practice of liquid biopsy, with China and the United States being the leading contributors. Institutions such as Harvard University and the University of California system play a central role in the global collaboration network. Cancers has become the primary publication outlet for the field, while highly cited journals like Clinical Cancer Research play a crucial role in advancing its development. Keyword analysis reveals that research has progressively expanded into clinical applications, personalized treatment, and prognostic evaluation. Discussion Overall, as technology and applications continue to mature, liquid biopsy is expected to play an even greater role in the early diagnosis, treatment evaluation, and personalized treatment of cancer and other diseases.
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Affiliation(s)
- Shuo Zhang
- College of New Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hongwei Zhao
- Department of Third Cardre’s Ward, General Hospital of Northern Theater Command, Shenyang, China
| | - Kangchun Wang
- School of Medicine, Southeast University, Nanjing, China
| | - Lijie Li
- Department of Ultrasound, Liaocheng People’s Hospital, Liaocheng, China
| | - Qi Pan
- Department of Organ Transplantation and Hepatobiliary, The First Affiliated Hospital of China Medical University, Shenyang, China
- The Key Laboratory of Organ Transplantation in Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Meitong Lu
- Department of Third Cardre’s Ward, General Hospital of Northern Theater Command, Shenyang, China
| | - Xing Zhang
- Department of Third Cardre’s Ward, General Hospital of Northern Theater Command, Shenyang, China
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Zhao C, Lee YT, Melehy A, Kim M, Yang JZ, Zhang C, Kim J, Zhang RY, Lee J, Kim H, Ju Y, Tsai YJ, Zhou XJ, Han SHB, Sadeghi S, Finn RS, Saab S, Lu DS, Chiang J, Park JH, Brennan TV, Wisel SA, Alsudaney M, Kuo A, Ayoub WS, Kim H, Trivedi HD, Wang Y, Vipani A, Kim IK, Todo T, Steggerda JA, Voidonikolas G, Kosari K, Nissen NN, Saouaf R, Singal AG, Sim MS, Elashoff DA, You S, Agopian VG, Yang JD, Tseng HR, Zhu Y. Extracellular vesicle digital scoring assay for assessment of treatment responses in hepatocellular carcinoma patients. J Exp Clin Cancer Res 2025; 44:136. [PMID: 40307890 PMCID: PMC12044846 DOI: 10.1186/s13046-025-03379-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 03/29/2025] [Indexed: 05/02/2025] Open
Abstract
BACKGROUND There are no validated biomarkers for assessing hepatocellular carcinoma (HCC) treatment response (TR). Extracellular vesicles (EVs) are promising circulating biomarkers that may detect minimal residual disease in patients with treated HCC. METHODS We developed the HCC EV TR Score using HCC EV Digital Scoring Assay involving click chemistry-mediated enrichment of HCC EVs, followed by absolute quantification of HCC EV-specific genes by RT-digital PCR. Six HCC EV-specific genes were selected and validated through i) a comprehensive data analysis pipeline with an unprecedentedly large collection of liver transcriptome datasets (n = 9,160), ii) RNAscope validation on HCC tissues (n = 6), and iii) a pilot study on early- or intermediate-stage HCC and liver cirrhosis patients (n = 70). The performance of HCC EV TR Score was assessed in a phase-2 retrospective case-control study (n = 100). RESULTS HCC EV TR Scores, calculated from pre- and post-treatment plasma samples in the phase-2 case-control study, accurately differentiated post-treatment viable from nonviable HCC in the training (area under the ROC curve [AUROC] of 0.90, n = 49) and validation set (AUROC of 0.88, n = 51). At an optimal cutoff of 0.76 identified in the training set, HCC EV TR Score had high accuracy in detecting viable tumors (sensitivity: 76.5%, specificity: 88.2%) and found residual disease not initially observed on MRI in six patients with a median lead time of 63 days. CONCLUSIONS This EV-based digital scoring approach shows great promise to augment cross-sectional imaging for the assessment of HCC treatment response.
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Grants
- U01 CA230705 NCI NIH HHS
- K08 CA259534 NCI NIH HHS
- R21 CA280444 NCI NIH HHS
- R01 CA255727 NCI NIH HHS
- R01CA277530, R01CA255727, R01CA253651, R01CA253651-04S1, R21CA280444, R01CA246304, U01EB026421, K08CA259534, R44CA288163, U01CA271887, and U01CA230705 NCI NIH HHS
- U01 EB026421 NIBIB NIH HHS
- U01 CA271887 NCI NIH HHS
- R44 CA288163 NCI NIH HHS
- R01 CA277530 NCI NIH HHS
- R01 CA253651 NCI NIH HHS
- R01 CA246304 NCI NIH HHS
- National Cancer Institute
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Affiliation(s)
- Chen Zhao
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
- Department of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China
| | - Yi-Te Lee
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Andrew Melehy
- Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - Minhyung Kim
- Department of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Jacqueline Ziqian Yang
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
- Department of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - Ceng Zhang
- Department of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - Jina Kim
- Department of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Ryan Y Zhang
- Department of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - Junseok Lee
- Department of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - Hyoyong Kim
- Department of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - Yong Ju
- Department of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - Yuan-Jen Tsai
- Department of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, 110301, Taiwan
| | - Xianghong Jasmine Zhou
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - Steven-Huy B Han
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angles (UCLA), Los Angeles, CA, 90095, USA
| | - Saeed Sadeghi
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angles (UCLA), Los Angeles, CA, 90095, USA
| | - Richard S Finn
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angles (UCLA), Los Angeles, CA, 90095, USA
| | - Sammy Saab
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angles (UCLA), Los Angeles, CA, 90095, USA
| | - David S Lu
- Department of Interventional Radiology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - Jason Chiang
- Department of Interventional Radiology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - Jae-Ho Park
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Todd V Brennan
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Steven A Wisel
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Manaf Alsudaney
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Alexander Kuo
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Walid S Ayoub
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Hyunseok Kim
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Hirsh D Trivedi
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Yun Wang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Aarshi Vipani
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Irene K Kim
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Tsuyoshi Todo
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Justin A Steggerda
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Georgios Voidonikolas
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Kambiz Kosari
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Nicholas N Nissen
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Rola Saouaf
- Department of Radiology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
| | - Amit G Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Myung Shin Sim
- Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA
| | - David A Elashoff
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angles (UCLA), Los Angeles, CA, 90095, USA
| | - Sungyong You
- Department of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
- Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
| | - Vatche G Agopian
- Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
- Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, 90048, USA.
| | - Hsian-Rong Tseng
- Department of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
| | - Yazhen Zhu
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
- Department of Molecular and Medical Pharmacology, California Nanosystems Institute, Crump Institute for Molecular Imaging, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles (UCLA), Los Angeles, CA, 90095, USA.
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Selvaggi F, Lopetuso LR, delli Pizzi A, Melchiorre E, Murgiano M, Taraschi AL, Cotellese R, Diana M, Vivarelli M, Mocchegiani F, Catalano T, Aceto GM. Diagnosis of Cholangiocarcinoma: The New Biological and Technological Horizons. Diagnostics (Basel) 2025; 15:1011. [PMID: 40310432 PMCID: PMC12025943 DOI: 10.3390/diagnostics15081011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 03/30/2025] [Accepted: 04/07/2025] [Indexed: 05/02/2025] Open
Abstract
The diagnosis of cholangiocarcinoma (CCA) remains challenging. Although new technologies have been developed and validated, their routine use in clinical practice is needed. Conventional cytology obtained during endoscopic retrograde cholangiopancreatography-guided brushings is the first-line technique for the diagnosis of CCA, but it has shown limited sensitivity when combined with endoscopic ultrasound-guided biopsy. Other diagnostic tools have been proposed for the diagnosis of CCA, with their respective advantages and limitations. Cholangioscopy with biopsy or cytology combined with FISH analysis, intraductal biliary ultrasound and confocal laser microscopy have made significant advances in the last decade. More recently, developments in the analytical "omics" sciences have allowed the mapping of the microbiota of patients with CCA, and liquid biopsy with proteomic and extracellular vesicle analysis has allowed the identification of new biomarkers that can be incorporated into the predictive diagnostics. Furthermore, in the preoperative setting, radiomics, radiogenomics and the integrated use of artificial intelligence may provide new useful foundations for integrated diagnosis and personalized therapy for hepatobiliary diseases. This review aims to evaluate the current diagnostic approaches and innovative translational research that can be integrated for the diagnosis of CCA.
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Affiliation(s)
- Federico Selvaggi
- ASL2 Lanciano-Vasto-Chieti, Unit of General Surgery, 66100 Chieti, Italy
- Villa Serena Foundation for Research, 65013 Città Sant’Angelo, Italy; (R.C.); (G.M.A.)
| | - Loris Riccardo Lopetuso
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Gemelli IRCCS, 00136 Roma, Italy; (L.R.L.); (M.M.)
- Dipartimento di Scienze della Vita della Salute e delle Professioni Sanitarie, Università degli Studi Link, 00165 Roma, Italy
| | - Andrea delli Pizzi
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio”, 66100 Chieti, Italy;
- ITAB—Institute for Advanced Biomedical Technologies, University “G. d’Annunzio”, 66100 Chieti, Italy
| | - Eugenia Melchiorre
- University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy;
| | - Marco Murgiano
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Gemelli IRCCS, 00136 Roma, Italy; (L.R.L.); (M.M.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Roma, Italy
| | | | - Roberto Cotellese
- Villa Serena Foundation for Research, 65013 Città Sant’Angelo, Italy; (R.C.); (G.M.A.)
| | - Michele Diana
- Department of Surgery, University Hospital of Geneva, 1205 Geneva, Switzerland;
| | - Marco Vivarelli
- Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126 Ancona, Italy; (M.V.); (F.M.)
| | - Federico Mocchegiani
- Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126 Ancona, Italy; (M.V.); (F.M.)
| | - Teresa Catalano
- Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy;
| | - Gitana Maria Aceto
- Villa Serena Foundation for Research, 65013 Città Sant’Angelo, Italy; (R.C.); (G.M.A.)
- Department of Science, University “G. d’Annunzio” Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy
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5
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Tang R, Luo S, Liu H, Sun Y, Liu M, Li L, Ren H, Angele MK, Börner N, Yu K, Guo Z, Yin G, Luo H. Circulating Tumor Microenvironment in Metastasis. Cancer Res 2025; 85:1354-1367. [PMID: 39992721 PMCID: PMC11997552 DOI: 10.1158/0008-5472.can-24-1241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 11/12/2024] [Accepted: 02/19/2025] [Indexed: 02/26/2025]
Abstract
Activation of invasion and metastasis is a central hallmark of cancer, contributing to the primary cause of death for patients with cancer. In the multistep metastatic process, cancer cells must infiltrate the circulation, survive, arrest at capillary beds, extravasate, and form metastatic clones in distant organs. However, only a small proportion of circulating tumor cells (CTC) successfully form metastases, with transit of CTCs in the circulation being the rate-limiting step. The fate of CTCs is influenced by the circulating tumor microenvironment (cTME), which encompasses factors affecting their biological behaviors in the circulation. This liquid and flowing microenvironment differs significantly from the primary TME or the premetastatic niche. This review summarizes the latest advancements in identifying the biophysical cues, key components, and biological roles of the cTME, highlighting the network among biophysical attributes, blood cells, and nonblood factors in cancer metastasis. In addition to the potential of the cTME as a therapeutic target for inhibiting metastasis, the cTME could also represent as a biomarker for predicting patient outcomes and developing strategies for treating cancer.
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Affiliation(s)
- Rui Tang
- Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Shujuan Luo
- Department of Obstetrics, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
| | - Hui Liu
- Department of Thyroid and Breast Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yan Sun
- Department of Cell Biology and Medical Genetics, Basic Medical School, Chongqing Medical University, Chongqing, China
| | - Manran Liu
- Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Lu Li
- Department of Thyroid and Breast Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Haoyu Ren
- Department of Thyroid and Breast Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Martin K. Angele
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich Munich, Germany
| | - Nikolaus Börner
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich Munich, Germany
| | - Keda Yu
- Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai, P.R. China
| | - Zufeng Guo
- Center for Novel Target and Therapeutic Intervention, Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Guobing Yin
- Department of Thyroid and Breast Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Haojun Luo
- Department of Thyroid and Breast Surgery, Renji Hospital, School of Medicine, Chongqing University, Chongqing, China
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6
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Xu Y, Xu L, Chen Q, Zou C, Huang J, Zhang L. Crosstalk between exosomes and tumor-associated macrophages in hepatocellular carcinoma: implication for cancer progression and therapy. Front Immunol 2025; 16:1512480. [PMID: 40264760 PMCID: PMC12011854 DOI: 10.3389/fimmu.2025.1512480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 02/26/2025] [Indexed: 04/24/2025] Open
Abstract
Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, represents a significant cause of cancer-related mortality. While our understanding of its pathogenesis is comparatively comprehensive, the influence of the tumor microenvironment (TME) on its progression warrants additional investigation. Tumor-associated macrophages (TAMs) have significant impacts on cancer cell proliferation, migration, invasion, and immune response, facilitating a complex interaction within the TME. Exosomes, which measure between 30 and 150 nanometers in size, are categorized into small extracellular vesicles, secreted by a wide range of eukaryotic cells. They can transfer biological molecules including proteins, non-coding RNAs, and lipids, which mediates the intercellular communication within the TME. Emerging evidence has revealed that exosomes regulate macrophage polarization, thus impacting cancer progression and immune responses within the TME of HCC. Moreover, TAM-derived exosomes also play crucial roles in malignant transformation, which hold immense potential for cancer therapy. In this review, we elaborate on the crosstalk between exosomes and TAMs within TME during HCC development. Moreover, we delve into the feasible treatment approaches for exosomes in cancer therapy and emphasize the limitations and challenges for the translation of exosomes derived from TAMs into clinical courses for cancer therapy, which may provide new perspectives on further ameliorations of therapeutic regimes based on exosomes to advance their clinical applications.
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Affiliation(s)
- Ying Xu
- Department of Anesthesiology Operating Room, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Linyue Xu
- School of Sports Medicine and Health, Chengdu Sport University, Chengdu, China
| | - Qiuyan Chen
- School of Sports Medicine and Health, Chengdu Sport University, Chengdu, China
| | - Can Zou
- School of Sports Medicine and Health, Chengdu Sport University, Chengdu, China
| | - Ju Huang
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Limei Zhang
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
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7
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Park J, Lee YT, Agopian VG, Liu JS, Koltsova EK, You S, Zhu Y, Tseng HR, Yang JD. Liquid biopsy in hepatocellular carcinoma: Challenges, advances, and clinical implications. Clin Mol Hepatol 2025; 31:S255-S284. [PMID: 39604328 PMCID: PMC11925447 DOI: 10.3350/cmh.2024.0541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 11/15/2024] [Accepted: 11/25/2024] [Indexed: 11/29/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional's skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.
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Affiliation(s)
- Jaeho Park
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Yi-Te Lee
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Vatche G. Agopian
- Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA
- Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA
| | - Jessica S Liu
- Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
| | - Ekaterina K. Koltsova
- Smidt Heart Institute, Department of Medicine, Department of Biomedical Sciences, 8700 Beverly Blvd, Los Angeles, CA, USA
| | - Sungyong You
- Department of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Yazhen Zhu
- Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA
- California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA
| | - Hsian-Rong Tseng
- Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA
- California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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8
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Mansouri S. Emerging biosensing platforms based on metal-organic frameworks (MOFs) for detection of exosomes as diagnostic cancer biomarkers: case study for the role of the MOFs. J Mater Chem B 2025; 13:1586-1598. [PMID: 39745316 DOI: 10.1039/d4tb02465f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Exosomes, which are considered nanoscale extracellular vesicles (EVs), are secreted by various cell types and widely distributed in different biological fluids. They consist of multifarious bioactive molecules and use systematic circulation for their transfer to adjoining cells. This phenomenon enables exosomes to take part in intercellular and intracellular communications. They serve as novel and important cancer biomarkers due to their ability to be obtained from various biological fluids and the presence of nucleic acids, proteins, glycoconjugates, and lipids in their structure. The advancement of sensitive and selective exosome detection approaches continues to be a critical challenge that must be addressed. Metal-organic frameworks (MOFs) are a class of 2D and 3D synthetic organic and crystalline nanomaterials, forming through the self-assembly of organic linking molecules and metal ions. The exploration of MOF-based molecules in the recognition of exosomes is an essential aspect in the development of cutting-edge sensing platforms due to their tunable pore structures, excellent adsorption capabilities, and high surface area. Their advantages allow for the inclusion of a large number of electroactive molecules and biological elements, thereby enhancing their electrical conductivity and selectivity, respectively. The synergetic effect of nanomaterials and bioreceptors allows for efficient detection probes. In this review, the different roles of MOFs in the biosensing of exosomes are highlighted, providing a comprehensive understanding of biosensing approaches in this area. In addition, probes based on MOFs and different bioreceptors are investigated for detecting these important cancer biomarkers. The current gaps in this field and future perspectives are discussed.
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Affiliation(s)
- Sofiene Mansouri
- Department of Biomedical Technology, College of Applied Medical Sciences in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia.
- University of Tunis El Manar, Higher Institute of Medical Technologies of Tunis, Laboratory of Biophysics and Medical Technologies, Tunis, Tunisia
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9
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Solhi R, Pourhamzeh M, Zarrabi A, Hassan M, Mirzaei H, Vosough M. Novel biomarkers for monitoring and management of hepatocellular carcinoma. Cancer Cell Int 2024; 24:428. [PMID: 39719624 DOI: 10.1186/s12935-024-03600-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Accepted: 12/05/2024] [Indexed: 12/26/2024] Open
Abstract
Due to current challenges in the early detection, less than 40% of individuals diagnosed with hepatocellular carcinoma (HCC) are viable candidates for surgical intervention. Therefore, validating and launching of a novel precise diagnostic approach is essential for early diagnosis. Based on developing evidence using circulating tumor cells and their derivatives, circulating miRNAs, and extracellular vesicles (EVs), liquid biopsy may offer a reliable platform for the HCC's early diagnosis. Each liquid biopsy analyte may provide significant areas for diagnosis, prognostic assessment, and treatment monitoring of HCC patients depending on its kind, sensitivity, and specificity. The current review addresses potential clinical applications, current research, and future developments for liquid biopsy in HCC management.
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Affiliation(s)
- Roya Solhi
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Mahsa Pourhamzeh
- Departments of Pathology and Medicine, UC San Diego, La Jolla, CA, USA
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34396, Turkey
| | - Moustapha Hassan
- Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran.
| | - Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
- Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
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10
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Jin K, Lan H, Han Y, Qian J. Exosomes in cancer diagnosis based on the Latest Evidence: Where are We? Int Immunopharmacol 2024; 142:113133. [PMID: 39278058 DOI: 10.1016/j.intimp.2024.113133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 08/09/2024] [Accepted: 09/07/2024] [Indexed: 09/17/2024]
Abstract
Exosomes are small extracellular vesicles (EVs) derived from various cellular sources and have emerged as favorable biomarkers for cancer diagnosis and prognosis. These vesicles contain a variety of molecular components, including nucleic acids, proteins, and lipids, which can provide valuable information for cancer detection, classification, and monitoring. However, the clinical application of exosomes faces significant challenges, primarily related to the standardization and scalability of their use. In order to overcome these challenges, sophisticated methods such as liquid biopsy and imaging are being combined to augment the diagnostic capabilities of exosomes. Additionally, a deeper understanding of the interaction between exosomes and immune system components within the tumor microenvironment (TME) is essential. This review discusses the biogenesis and composition of exosomes, addresses the current challenges in their clinical translation, and highlights recent technological advancements and integrative approaches that support the role of exosomes in cancer diagnosis and prognosis.
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Affiliation(s)
- Ketao Jin
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310003, China.
| | - Huanrong Lan
- Department of Surgical Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, China; Department of Breast Surgery, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang 310006, China.
| | - Yuejun Han
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310003, China
| | - Jun Qian
- Department of Colorectal Surgery, Xinchang People's Hospital, Affiliated Xinchang Hospital, Wenzhou Medical University, Xinchang, Zhejiang 312500, China.
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11
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Ma L, Guo H, Zhao Y, Liu Z, Wang C, Bu J, Sun T, Wei J. Liquid biopsy in cancer current: status, challenges and future prospects. Signal Transduct Target Ther 2024; 9:336. [PMID: 39617822 PMCID: PMC11609310 DOI: 10.1038/s41392-024-02021-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/10/2024] [Accepted: 10/14/2024] [Indexed: 12/06/2024] Open
Abstract
Cancer has a high mortality rate across the globe, and tissue biopsy remains the gold standard for tumor diagnosis due to its high level of laboratory standardization, good consistency of results, relatively stable samples, and high accuracy of results. However, there are still many limitations and drawbacks in the application of tissue biopsy in tumor. The emergence of liquid biopsy provides new ideas for early diagnosis and prognosis of tumor. Compared with tissue biopsy, liquid biopsy has many advantages in the diagnosis and treatment of various types of cancer, including non-invasive, quickly and so on. Currently, the application of liquid biopsy in tumor detection has received widely attention. It is now undergoing rapid progress, and it holds significant potential for future applications. Around now, liquid biopsies encompass several components such as circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. In addition, advances in the identification of liquid biopsy indicators have significantly enhanced the possibility of utilizing liquid biopsies in clinical settings. In this review, we will discuss the application, advantages and challenges of liquid biopsy in some common tumors from the perspective of diverse systems of tumors, and look forward to its future development prospects in the field of cancer diagnosis and treatment.
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Affiliation(s)
- Liwei Ma
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China.
| | - Huiling Guo
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Yunxiang Zhao
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhibo Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Chenran Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Jiahao Bu
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Ting Sun
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China.
| | - Jianwei Wei
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
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12
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Ma Y, Zhang X, Liu C, Zhao Y. Extracellular vesicles in cancers: mechanisms, biomarkers, and therapeutic strategies. MedComm (Beijing) 2024; 5:e70009. [PMID: 39611045 PMCID: PMC11604295 DOI: 10.1002/mco2.70009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 10/03/2024] [Accepted: 10/10/2024] [Indexed: 11/30/2024] Open
Abstract
Extracellular vesicles (EVs) composed of various biologically active constituents, such as proteins, nucleic acids, lipids, and metabolites, have emerged as a noteworthy mode of intercellular communication. There are several categories of EVs, including exosomes, microvesicles, and apoptotic bodies, which largely differ in their mechanisms of formation and secretion. The amount of evidence indicated that changes in the EV quantity and composition play a role in multiple aspects of cancer development, such as the transfer of oncogenic signals, angiogenesis, metabolism remodeling, and immunosuppressive effects. As EV isolation technology and characteristics recognition improve, EVs are becoming more commonly used in the early diagnosis and evaluation of treatment effectiveness for cancers. Actually, EVs have sparked clinical interest in their potential use as delivery vehicles or vaccines for innovative antitumor techniques. This review will focus on the function of biological molecules contained in EVs linked to cancer progression and their participation in the intricate interrelationship within the tumor microenvironment. Furthermore, the potential efficacy of an EV-based liquid biopsy and delivery cargo for treatment will be explored. Finally, we explicitly delineate the limitations of EV-based anticancer therapies and provide an overview of the clinical trials aimed at improving EV development.
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Affiliation(s)
- Yuxi Ma
- Cancer CenterUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Hubei Key Laboratory of Precision Radiation OncologyWuhanChina
- Cancer CenterInstitute of Radiation OncologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Xiaohui Zhang
- Cancer CenterHubei Key Laboratory of Cell HomeostasisCollege of Life SciencesTaiKang Center for Life and Medical SciencesWuhan UniversityWuhanChina
| | - Cuiwei Liu
- Cancer CenterUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Hubei Key Laboratory of Precision Radiation OncologyWuhanChina
- Cancer CenterInstitute of Radiation OncologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Yanxia Zhao
- Cancer CenterUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Hubei Key Laboratory of Precision Radiation OncologyWuhanChina
- Cancer CenterInstitute of Radiation OncologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
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13
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Zhou Z, Zhang R, Zhou A, Lv J, Chen S, Zou H, Zhang G, Lin T, Wang Z, Zhang Y, Weng S, Han X, Liu Z. Proteomics appending a complementary dimension to precision oncotherapy. Comput Struct Biotechnol J 2024; 23:1725-1739. [PMID: 38689716 PMCID: PMC11058087 DOI: 10.1016/j.csbj.2024.04.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 04/11/2024] [Accepted: 04/17/2024] [Indexed: 05/02/2024] Open
Abstract
Recent advances in high-throughput proteomic profiling technologies have facilitated the precise quantification of numerous proteins across multiple specimens concurrently. Researchers have the opportunity to comprehensively analyze the molecular signatures in plentiful medical specimens or disease pattern cell lines. Along with advances in data analysis and integration, proteomics data could be efficiently consolidated and employed to recognize precise elementary molecular mechanisms and decode individual biomarkers, guiding the precision treatment of tumors. Herein, we review a broad array of proteomics technologies and the progress and methods for the integration of proteomics data and further discuss how to better merge proteomics in precision medicine and clinical settings.
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Affiliation(s)
- Zhaokai Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan 450052, China
| | - Ruiqi Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Aoyang Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Jinxiang Lv
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Shuang Chen
- Center of Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Haijiao Zou
- Center of Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Ge Zhang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Ting Lin
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Zhan Wang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan 450052, China
| | - Yuyuan Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Siyuan Weng
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Xinwei Han
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Interventional Institute of Zhengzhou University, Zhengzhou, Henan 450052, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Zaoqu Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Interventional Institute of Zhengzhou University, Zhengzhou, Henan 450052, China
- Interventional Treatment and Clinical Research Center of Henan Province, Zhengzhou, Henan 450052, China
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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14
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Alvarado-Tapias E, Maya-Miles D, Albillos A, Aller R, Ampuero J, Andrade RJ, Arechederra M, Aspichueta P, Banales JM, Blas-García A, Caparros E, Cardoso Delgado T, Carrillo-Vico A, Claria J, Cubero FJ, Díaz-Ruiz A, Fernández-Barrena MG, Fernández-Iglesias A, Fernández-Veledo S, Francés R, Gallego-Durán R, Gracia-Sancho J, Irimia M, Lens S, Martínez-Chantar ML, Mínguez B, Muñoz-Hernández R, Nogueiras R, Ramos-Molina B, Riveiro-Barciela M, Rodríguez-Perálvarez ML, Romero-Gómez M, Sabio G, Sancho-Bru P, Ventura-Cots M, Vidal S, Gahete MD. Proceedings of the 5th Meeting of Translational Hepatology, organized by the Spanish Association for the Study of the Liver (AEEH). GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:502207. [PMID: 38723772 DOI: 10.1016/j.gastrohep.2024.502207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 05/02/2024] [Indexed: 11/30/2024]
Abstract
This is the summary report of the 5th Translational Hepatology Meeting, endorsed by the Spanish Association for the Study of the Liver (AEEH) and held in Seville, Spain, in October 2023. The meeting aimed to provide an update on the latest advances in the field of basic and translational hepatology, covering different molecular, cellular, and pathophysiological aspects of the most relevant clinical challenges in liver pathologies. This includes the identification of novel biomarkers and diagnostic tools, the understanding of the relevance of immune response and inflammation in liver diseases, the characterization of current medical approaches to reverse liver diseases, the incorporation of novel molecular insights through omics techniques, or the characterization of the impact of toxic and metabolic insults, as well as other organ crosstalk, in liver pathophysiology.
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Affiliation(s)
- Edilmar Alvarado-Tapias
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Department of Gastroenterology, Hospital Santa Creu I Sant Pau, Institut de Recerca Sant Pau, Universidad Autónoma de Barcelona, Barcelona, Spain.
| | - Douglas Maya-Miles
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CISC, Universidad de Sevilla, Sevilla, Spain.
| | - Agustin Albillos
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal/Universidad de Alcalá/Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Rocio Aller
- BioCritic, Group for Biomedical Research in Critical Care Medicine, Spain; Department of Medicine, Dermatology and Toxicology, Universidad de Valladolid, Spain; Gastroenterology Unit, Hospital Clínico Universitario de Valladolid, 47003 Valladolid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
| | - Javier Ampuero
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CISC, Universidad de Sevilla, Sevilla, Spain
| | - Raul J Andrade
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
| | - Maria Arechederra
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain
| | - Patricia Aspichueta
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain; Biobizkaia Health Research Institute, Barakaldo, Spain
| | - Jesus M Banales
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute - Donostia University Hospital - University of the Basque Country (UPV/EHU), Ikerbasque, Donostia-San Sebastian, Spain; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Ana Blas-García
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Departamento de Fisiología, Universitat de València, Av. Blasco Ibáñez, 15, 46010 Valencia, Spain; FISABIO (Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana), Av. de Catalunya, 21, 46020 Valencia, Spain
| | - Esther Caparros
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Grupo de Inmunobiología Hepática e Intestinal, Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain; Instituto de Investigación Sanitaria ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain
| | - Teresa Cardoso Delgado
- Biobizkaia Health Research Institute, Barakaldo, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
| | - Antonio Carrillo-Vico
- Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CISC, Universidad de Sevilla, Sevilla, Spain; Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Sevilla, Seville, Spain
| | - Joan Claria
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Biochemistry and Molecular Genetics Service, Hospital Clínic, IDIBAPS, Barcelona, Spain; University of Barcelona, Spain
| | - Francisco Javier Cubero
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain; Health Research Institute Gregorio Marañón (IiSGM), Madrid, Spain
| | - Alberto Díaz-Ruiz
- Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging, Madrid Institute for Advanced Studies - IMDEA Food, CEI UAM+CSIC, Madrid, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Madrid, Spain
| | - Maite G Fernández-Barrena
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain; Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Spain
| | - Anabel Fernández-Iglesias
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Liver Vascular Biology Research Group, IDIBAPS, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
| | - Sonia Fernández-Veledo
- Department of Endocrinology and Nutrition and Research Unit, University Hospital of Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili (URV), Tarragona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Ruben Francés
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Grupo de Inmunobiología Hepática e Intestinal, Departamento Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain; Instituto de Investigación Sanitaria ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain
| | - Rocío Gallego-Durán
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CISC, Universidad de Sevilla, Sevilla, Spain
| | - Jordi Gracia-Sancho
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Liver Vascular Biology Research Group, IDIBAPS, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
| | - Manuel Irimia
- Universitat Pompeu Fabra (UPF), Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, ICREA, Barcelona, Spain
| | - Sabela Lens
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain; Liver Unit, Hospital Clínic, IDIBAPS, Barcelona, Spain
| | - María Luz Martínez-Chantar
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain
| | - Beatriz Mínguez
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Rocío Muñoz-Hernández
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CISC, Universidad de Sevilla, Sevilla, Spain; Departamento de fisiología, Facultad de Biología, Universidad de Sevilla, Sevilla, Spain
| | - Rubén Nogueiras
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Madrid, Spain; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; Galician Agency of Innovation (GAIN), Xunta de Galicia, Santiago de Compostela, Spain
| | - Bruno Ramos-Molina
- Obesity, Diabetes and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB), Murcia, Spain
| | - Mar Riveiro-Barciela
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Manuel L Rodríguez-Perálvarez
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Department of Hepatology and Liver Transplantation, Reina Sofia University Hospital, Cordoba, Spain; Maimonides Biomedical Research Institute of Córdoba (IMIBIC), University of Córdoba, Cordoba, Spain
| | - Manuel Romero-Gómez
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CISC, Universidad de Sevilla, Sevilla, Spain
| | - Guadalupe Sabio
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Stress Kinases in Diabetes, Cancer and Biochemistry, Spain; Centro Nacional de Investigaciones Oncologicas (CNIO), Organ Crosstalk in Metabolic Diseases, Madrid, Spain
| | - Pau Sancho-Bru
- CIBEREHD (Center for Biomedical Network Research in Liver and Digestive Diseases), Instituto de Salud Carlos III, 28029 Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Meritxell Ventura-Cots
- Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Center for Liver Diseases, Pittsburgh Liver Research Center, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Silvia Vidal
- Group of Inflammatory Diseases, Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
| | - Manuel D Gahete
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Madrid, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Spain; Molecular Hepatology Group, Maimonides Biomedical Research Institute of Córdoba (IMIBIC), Spain; Reina Sofia University Hospital, Cordoba, Spain.
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15
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Valero P, Silva K, Valenzuela-Hinrichsen A, Vásquez A, Espinoza F, Lira F, Cornejo M, Fuentes G, González D, Moore-Carrasco R, van der Beek EM, Hillebrands JL, van Goor H, Grismaldo A, Sobrevia L. Shortcomings, limitations and gaps in physiological roles of extracellular vesicles in obesity. J Physiol 2024. [PMID: 39470472 DOI: 10.1113/jp286955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 10/04/2024] [Indexed: 10/30/2024] Open
Abstract
Extracellular vesicles (EVs) play a crucial role in mediating communication between cells across species and kingdoms. The intercellular communication facilitated by EVs through autocrine and paracrine signalling mechanisms is essential for cell survival, maintaining normal metabolic functions and ensuring overall bodily homeostasis and health. Extracellular vesicles are present in various bodily fluids, such as pleural effusions, plasma, breast milk, amniotic fluid, semen and saliva. Additionally, the generation and release of EVs contribute to the removal of cellular waste. Patients with obesity exhibit a higher release and amount of circulating EVs than individuals with normal weight. This increased EV release in obesity might contribute to the inflammatory state characteristic of this metabolic condition, because higher levels of pro-inflammatory molecules are found within their cargo. However, interpreting results related to EV abundance, cargo and biological actions can be complicated by several factors; these include variations in cell sources, a wide age range (from children to the elderly), a mix of females and males, medication use and health status, a range of body weights (from normal weight to morbid obesity) and differences between in vitro assays using cell lines versus primary cultures. This article addresses the shortcomings, limitations and gaps in knowledge, providing a framework for enhancing our understanding of the physiological effects of EVs on obesity.
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Affiliation(s)
- Paola Valero
- **Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Faculty of Health Sciences, Universidad de Talca, Talca, Chile
| | - Katherin Silva
- **Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Institute of Chemistry, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
| | - Andrés Valenzuela-Hinrichsen
- **Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Antonia Vásquez
- **Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Fernanda Espinoza
- **Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Fernanda Lira
- Faculty of Medicine, Universidad de Antofagasta, Antofagasta, Chile
| | - Marcelo Cornejo
- **Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Faculty of Health Sciences, Universidad de Talca, Talca, Chile
- Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Centre Groningen (UMCG), Groningen, The Netherlands
- Biomedical Department, Faculty of Health Sciences, Universidad de Antofagasta, Antofagasta, Chile
| | - Gonzalo Fuentes
- **Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Faculty of Health Sciences, Universidad de Talca, Talca, Chile
- Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Centre Groningen (UMCG), Groningen, The Netherlands
| | - Daniel González
- Faculty of Health Sciences, Universidad de Talca, Talca, Chile
| | | | - Eline M van der Beek
- Department of Pediatrics, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands
- Nestlé Institute for Health Sciences, Nestlé Research, Societé des Produits de Nestlé, Lausanne, Switzerland
| | - Jan-Luuk Hillebrands
- Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Centre Groningen (UMCG), Groningen, The Netherlands
| | - Harry van Goor
- Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Centre Groningen (UMCG), Groningen, The Netherlands
| | - Adriana Grismaldo
- **Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- **Faculty of Excellence program, School of Medicine and Health Sciences, The Institute for Obesity Research (IOR), Eutra, Tecnologico de Monterrey, Monterrey, Nuevo León, Mexico
| | - Luis Sobrevia
- **Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
- Department of Pathology and Medical Biology, Division of Pathology, University of Groningen, University Medical Centre Groningen (UMCG), Groningen, The Netherlands
- **Faculty of Excellence program, School of Medicine and Health Sciences, The Institute for Obesity Research (IOR), Eutra, Tecnologico de Monterrey, Monterrey, Nuevo León, Mexico
- Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville, Spain
- Medical School (Faculty of Medicine), Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
- University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, Queensland, Australia
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16
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Egerer M, Schuch K, Schöler D, Artusa F, Püngel T, Holtman TM, Loosen SH, Demir M, Wree A, Luedde T, Tacke F, Roderburg C, Mohr R. Extracellular Vesicles May Predict Response to Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:3651. [PMID: 39518089 PMCID: PMC11545167 DOI: 10.3390/cancers16213651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 10/24/2024] [Accepted: 10/27/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND AND AIMS Treatment with atezolizumab and bevacizumab has been approved as one of the standards of care for patients with advanced hepatocellular carcinoma (HCC). The median overall survival (OS) upon available treatments still remains below 2 years, urgently suggesting better stratification tools to identify ideal candidates for this treatment and potentially allowing personalized approaches. In this study, we evaluated the potential role of extracellular vesicles (EVs) as a novel biomarker in patients receiving atezolizumab and bevacizumab for HCC. METHODS We characterized EVs in 212 longitudinal serum samples from an observational cohort of 53 individuals with advanced HCC, who started therapy with atezolizumab plus bevacizumab at our center between January 2020 and March 2022. RESULTS In our cohort, the overall efficacy of atezolizumab and bevacizumab was comparable to previously published phase III data. We detected significantly smaller EVs in treatment responders, while enlarged EVs were associated with significantly decreased efficacy of atezolizumab and bevacizumab in terms of OS. A decrease in vesicle size during immunotherapy was related to a longer progression-free survival (PFS). A univariate Cox regression analysis including various clinicopathological parameters (e.g., tumor stage, markers of inflammation, organ dysfunction, or tumor markers) revealed vesicle size as an independent prognostic marker in HCC patients receiving atezolizumab and bevacizumab. Moreover, higher vesicle concentrations and lower zeta potentials were identified as a positive prognostic factor throughout treatment. CONCLUSIONS Distinct EV characteristics such as vesicle size, concentration, and zeta potential represent promising novel biomarkers in patients with advanced HCC receiving atezolizumab and bevacizumab, potentially helping to identify optimal candidates for checkpoint inhibitor-based treatments.
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Affiliation(s)
- Mara Egerer
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.E.); (F.A.); (T.P.); (T.M.H.); (M.D.); (A.W.); (F.T.)
| | - Kathrin Schuch
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany; (K.S.); (D.S.); (S.H.L.); (T.L.); (C.R.)
| | - David Schöler
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany; (K.S.); (D.S.); (S.H.L.); (T.L.); (C.R.)
| | - Fabian Artusa
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.E.); (F.A.); (T.P.); (T.M.H.); (M.D.); (A.W.); (F.T.)
| | - Tobias Püngel
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.E.); (F.A.); (T.P.); (T.M.H.); (M.D.); (A.W.); (F.T.)
- Berlin Institute of Health, 10178 Berlin, Germany
| | - Theresa Maria Holtman
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.E.); (F.A.); (T.P.); (T.M.H.); (M.D.); (A.W.); (F.T.)
| | - Sven H. Loosen
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany; (K.S.); (D.S.); (S.H.L.); (T.L.); (C.R.)
| | - Münevver Demir
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.E.); (F.A.); (T.P.); (T.M.H.); (M.D.); (A.W.); (F.T.)
| | - Alexander Wree
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.E.); (F.A.); (T.P.); (T.M.H.); (M.D.); (A.W.); (F.T.)
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany; (K.S.); (D.S.); (S.H.L.); (T.L.); (C.R.)
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.E.); (F.A.); (T.P.); (T.M.H.); (M.D.); (A.W.); (F.T.)
| | - Christoph Roderburg
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany; (K.S.); (D.S.); (S.H.L.); (T.L.); (C.R.)
| | - Raphael Mohr
- Department of Hepatology and Gastroenterology, Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM), Charité–Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; (M.E.); (F.A.); (T.P.); (T.M.H.); (M.D.); (A.W.); (F.T.)
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17
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Su L, Yue Y, Yan Y, Sun J, Meng L, Lu J, Zhang L, Liu J, Chi H, Liu S, Yang Z, Tang X. Extracellular vesicles in hepatocellular carcinoma: unraveling immunological mechanisms for enhanced diagnosis and overcoming drug resistance. Front Immunol 2024; 15:1485628. [PMID: 39530097 PMCID: PMC11550962 DOI: 10.3389/fimmu.2024.1485628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 10/08/2024] [Indexed: 11/16/2024] Open
Abstract
Current research is focused on utilizing EVs as a biopsy tool to improve the diagnostic accuracy of HCC, reduce surgical risk, and explore their potential in modulating drug resistance and advancing immunotherapeutic strategies. Extracellular vesicles (EVs) have been increasingly recognized as important non-invasive biomarkers in hepatocellular carcinoma (HCC) due to the presence of a variety of biomolecules within them, such as proteins and RNAs, etc. EVs play a key role in the early detection, diagnosis, treatment, and prognostic monitoring of HCC. These vesicles influence the development of HCC and therapeutic response in a variety of ways, including influencing the tumor microenvironment, modulating drug resistance, and participating in immune regulatory mechanisms. In addition, specific molecules such as miRNAs and specific proteins in EVs are regarded as potential markers for monitoring treatment response and recurrence of HCC, which have certain research space and development prospects. In this paper, we summarize the aspects of EVs as HCC diagnostic and drug resistance markers, and also discuss the questions that may be faced in the development of EVs as markers.
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Affiliation(s)
- Lanqian Su
- School of Clinical Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yuxin Yue
- Department of Pediatrics, Southwest Medical University, Luzhou, China
| | - Yalan Yan
- School of Clinical Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jianming Sun
- Department of General Surgery, Dazhou Central Hospital, Dazhou, China
| | - Lanxin Meng
- School of Clinical Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jiaan Lu
- School of Clinical Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Lanyue Zhang
- School of Clinical Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jie Liu
- Department of General Surgery, Dazhou Central Hospital, Dazhou, China
| | - Hao Chi
- School of Clinical Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Sinian Liu
- Department of Pathology, Xichong People’s Hospital, Nanchong, China
| | - Zhongqiu Yang
- Department of General Surgery, Dazhou Central Hospital, Dazhou, China
| | - Xiaowei Tang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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18
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Li D, Gao Y, Wang C, Hu L. Proteomic and phosphoproteomic profiling of urinary small extracellular vesicles in hepatocellular carcinoma. Analyst 2024; 149:4378-4387. [PMID: 38995156 DOI: 10.1039/d4an00660g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/13/2024]
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and a major cause of cancer-related mortality worldwide. Small extracellular vesicles (sEVs) are heterogeneous populations of membrane-structured vesicles that can be found in many biological fluids and are currently considered as a potential source of disease-associated biomarkers for diagnosis. The purpose of this study was to define the proteomic and phosphoproteomic landscape of urinary sEVs in patients with HCC. Mass spectrometry-based methods were used to detect the global proteome and phosphoproteome profiles of sEVs isolated by differential ultracentrifugation. Label-free quantitation analysis showed that 348 differentially expressed proteins (DEPs) and 548 differentially expressed phosphoproteins (DEPPs) were identified in the HCC group. Among them, multiple phosphoproteins related to HCC, including HSP90AA1, IQGAP1, MTOR, and PRKCA, were shown to be upregulated in the HCC group. Pathway enrichment analysis indicated that the upregulated DEPPs participate in the regulation of autophagy, proteoglycans in cancer, and the MAPK/mTOR/Rap1 signaling pathway. Furthermore, kinase-substrate enrichment analysis revealed activation of MTOR, AKT1, MAP2Ks, and MAPKs family kinases in HCC-derived sEVs, indicating that dysregulation of the MAPK and mTOR signaling pathways may be the primary sEV-mediated molecular mechanisms involved in the development and progression of HCC. This study demonstrated that urinary sEVs are enriched in proteomic and phosphoproteomic signatures that could be further explored for their potential use in early HCC diagnostic and therapeutic applications.
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Affiliation(s)
- Dejun Li
- Center for Supramolecular Chemical Biology, School of Life Sciences, Jilin University, Changchun 130012, China.
- Prenatal Diagnosis Center, Reproductive Medicine Center, The First Hospital of Jilin University, Changchun 130021, China
| | - Yujun Gao
- Center for Supramolecular Chemical Biology, School of Life Sciences, Jilin University, Changchun 130012, China.
| | - Chong Wang
- Department of Hepatology, The First Hospital of Jilin University, Changchun 130021, China.
| | - Lianghai Hu
- Center for Supramolecular Chemical Biology, School of Life Sciences, Jilin University, Changchun 130012, China.
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19
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Shen S, Wang C, Gu J, Song F, Wu X, Qian F, Chen X, Wang L, Peng Q, Xing Z, Gu L, Wang F, Cheng X. A Predictive Model for Initial Platinum-Based Chemotherapy Efficacy in Patients with Postoperative Epithelial Ovarian Cancer Using Tissue-Derived Small Extracellular Vesicles. J Extracell Vesicles 2024; 13:e12486. [PMID: 39104279 DOI: 10.1002/jev2.12486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 06/02/2024] [Accepted: 07/01/2024] [Indexed: 08/07/2024] Open
Abstract
Epithelial ovarian cancer (EOC) is an often-fatal malignancy marked by the development of resistance to platinum-based chemotherapy. Thus, accurate prediction of platinum drug efficacy is crucial for strategically selecting postoperative interventions to mitigate the risks associated with suboptimal therapeutic outcomes and adverse effects. Tissue-derived extracellular vesicles (tsEVs), in contrast to their plasma counterparts, have emerged as a powerful tool for examining distinctive attributes of EOC tissues. In this study, 4D data-independent acquisition (DIA) proteomic sequencing was performed on tsEVs obtained from 58 platinum-sensitive and 30 platinum-resistant patients with EOC. The analysis revealed a notable enrichment of differentially expressed proteins that were predominantly associated with immune-related pathways. Moreover, pivotal immune-related proteins (IRPs) were identified by LASSO regression. These factors, combined with clinical parameters selected through univariate logistic regression, were used for the construction of a model employing multivariate logistic regression. This model integrated three tsEV IRPs, CCR1, IGHV_35 and CD72, with one clinical parameter, the presence of postoperative residual lesions. Thus, this model could predict the efficacy of initial platinum-based chemotherapy in patients with EOC post-surgery, providing prognostic insights even before the initiation of chemotherapy.
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Affiliation(s)
- Shizhen Shen
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Department of Gynecologic Oncology, School of Medicine, Women's Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | - Conghui Wang
- Department of Gynecologic Oncology, School of Medicine, Women's Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiaxin Gu
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Feifei Song
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xiaodong Wu
- Department of Gynecologic Oncology, School of Medicine, Women's Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | - Fangfang Qian
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xiaojing Chen
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Lingfang Wang
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Qiaohua Peng
- Department of Gynecologic Oncology, School of Medicine, Women's Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | - Ziyu Xing
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Lingkai Gu
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Fenfen Wang
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Department of Gynecologic Oncology, School of Medicine, Women's Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xiaodong Cheng
- Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Department of Gynecologic Oncology, School of Medicine, Women's Hospital, Zhejiang University, Hangzhou, Zhejiang, China
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20
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Xu T, Lyu L, Zheng J, Li L. Advances in omics-based biomarker discovery for biliary tract malignancy Diagnosis:A narrative review. Mol Cell Probes 2024; 76:101970. [PMID: 38964426 DOI: 10.1016/j.mcp.2024.101970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 06/30/2024] [Accepted: 07/01/2024] [Indexed: 07/06/2024]
Abstract
Biliary tract neoplasms, which originate from the intrahepatic or extrahepatic biliary epithelium, are relatively rare but diagnostically challenging types of tumours, and their morbidity and mortality have increased in recent years. Due to ineffective early diagnostic methods, once detected, patients are in an advanced stage with a poor prognosis and few treatment options. With the development of omics technologies, the associations between microorganisms, bile acid and salts, noncoding RNAs and biliary tract malignancies have been gradually revealed, providing new methods for the discovery of diagnostic biomarkers. Here, we review the research advances in microbiomics, transcriptomics, metabolomics, and proteomics in the discovery of diagnostic biomarkers for biliary tract malignancies.
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Affiliation(s)
- Tao Xu
- Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 102200, China.
| | - Lingna Lyu
- Department of Hepatology and Gastroenterology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
| | - Junfu Zheng
- Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 102200, China.
| | - Lei Li
- Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 102200, China.
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21
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Sousa GC, Carvalho MG, Fonseca-Alves CE, Souza FF. Serum Extracellular Vesicles Cargo Approach in Bitches with Mammary Tumors. Curr Issues Mol Biol 2024; 46:7745-7768. [PMID: 39057100 PMCID: PMC11275879 DOI: 10.3390/cimb46070459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/11/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
This study investigated serum extracellular vesicles (EVs) in bitches with mammary neoplasms, in order to understand their size, shape, and concentration, as well as their association with tumor malignancy. Thirty bitches were categorized into control (n = 10), mammary tumor grades I and II (GI, n = 13), and grade III (GII, n = 7). Serum was separated from blood collected during mastectomy, and EVs were isolated using size exclusion chromatography. The analysis revealed no significant differences in EV concentrations among groups, with similar concentrations for control, GI, and GII. Ninety-one proteins were identified in EV-enriched samples, with six showing varied abundance across groups. Notably, keratin 18 was highly abundant in GI, while sushi domain-containing protein, EvC ciliary subunit 2, and the joining chain of multimeric IgM and IgA were increased in GII. Additionally, protocadherin 17 and albumin were upregulated in both GI and GII. ROC curves identified potential biomarkers for differentiating tumor grades. Enrichment pathway analysis revealed AFP gene upregulation in the GI. Mass spectrometry proteomics data were deposited in Mendeley Data. The study provides valuable insights into serum EV characterization in bitches, suggesting keratin 18 and protocadherin 17 as potential biomarkers for canine mammary neoplasia, with implications for future diagnostic and therapeutic strategies.
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Affiliation(s)
- Gabriela C. Sousa
- Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University, Unesp, Botucatu 18618-687, São Paulo, Brazil; (G.C.S.); (M.G.C.); (C.E.F.-A.)
- Department of Small Animal Clinical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, VA 24061, USA
| | - Marcos G. Carvalho
- Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University, Unesp, Botucatu 18618-687, São Paulo, Brazil; (G.C.S.); (M.G.C.); (C.E.F.-A.)
| | - Carlos E. Fonseca-Alves
- Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University, Unesp, Botucatu 18618-687, São Paulo, Brazil; (G.C.S.); (M.G.C.); (C.E.F.-A.)
| | - Fabiana F. Souza
- Department of Veterinary Surgery and Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University, Unesp, Botucatu 18618-687, São Paulo, Brazil; (G.C.S.); (M.G.C.); (C.E.F.-A.)
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22
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Fekry B, Ugartemendia L, Esnaola NF, Goetzl L. Extracellular Vesicles, Circadian Rhythms, and Cancer: A Comprehensive Review with Emphasis on Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:2552. [PMID: 39061191 PMCID: PMC11274441 DOI: 10.3390/cancers16142552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/12/2024] [Accepted: 07/14/2024] [Indexed: 07/28/2024] Open
Abstract
This review comprehensively explores the complex interplay between extracellular vesicles (ECVs)/exosomes and circadian rhythms, with a focus on the role of this interaction in hepatocellular carcinoma (HCC). Exosomes are nanovesicles derived from cells that facilitate intercellular communication by transporting bioactive molecules such as proteins, lipids, and RNA/DNA species. ECVs are implicated in a range of diseases, where they play crucial roles in signaling between cells and their surrounding environment. In the setting of cancer, ECVs are known to influence cancer initiation and progression. The scope of this review extends to all cancer types, synthesizing existing knowledge on the various roles of ECVs. A unique aspect of this review is the emphasis on the circadian-controlled release and composition of exosomes, highlighting their potential as biomarkers for early cancer detection and monitoring metastasis. We also discuss how circadian rhythms affect multiple cancer-related pathways, proposing that disruptions in the circadian clock can alter tumor development and treatment response. Additionally, this review delves into the influence of circadian clock components on ECV biogenesis and their impact on reshaping the tumor microenvironment, a key component driving HCC progression. Finally, we address the potential clinical applications of ECVs, particularly their use as diagnostic tools and drug delivery vehicles, while considering the challenges associated with clinical implementation.
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Affiliation(s)
- Baharan Fekry
- McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; (L.U.); (L.G.)
| | - Lierni Ugartemendia
- McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; (L.U.); (L.G.)
| | - Nestor F. Esnaola
- Division of Surgical Oncology and Gastrointestinal Surgery, Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA;
| | - Laura Goetzl
- McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; (L.U.); (L.G.)
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23
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Dabral P, Bhasin N, Ranjan M, Makhlouf MM, Abd Elmageed ZY. Tumor-Derived Extracellular Vesicles as Liquid Biopsy for Diagnosis and Prognosis of Solid Tumors: Their Clinical Utility and Reliability as Tumor Biomarkers. Cancers (Basel) 2024; 16:2462. [PMID: 39001524 PMCID: PMC11240796 DOI: 10.3390/cancers16132462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 06/26/2024] [Accepted: 07/02/2024] [Indexed: 07/16/2024] Open
Abstract
Early cancer detection and accurate monitoring are crucial to ensure increased patient survival. Recent research has focused on developing non-invasive biomarkers to diagnose cancer early and monitor disease progression at low cost and risk. Extracellular vesicles (EVs), nanosized particles secreted into extracellular spaces by most cell types, are gaining immense popularity as novel biomarker candidates for liquid cancer biopsy, as they can transport bioactive cargo to distant sites and facilitate intercellular communications. A literature search was conducted to discuss the current approaches for EV isolation and the advances in using EV-associated proteins, miRNA, mRNA, DNA, and lipids as liquid biopsies. We discussed the advantages and challenges of using these vesicles in clinical applications. Moreover, recent advancements in machine learning as a novel tool for tumor marker discovery are also highlighted.
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Affiliation(s)
- Prerna Dabral
- Vitalant Research Institute, University of California San Francisco, San Francisco, CA 94105, USA;
| | - Nobel Bhasin
- Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA;
| | - Manish Ranjan
- Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA;
| | - Maysoon M. Makhlouf
- Department of Biomedical Sciences, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine (VCOM), 4408 Bon Aire Drive, Monroe, LA 71203, USA;
| | - Zakaria Y. Abd Elmageed
- Department of Biomedical Sciences, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine (VCOM), 4408 Bon Aire Drive, Monroe, LA 71203, USA;
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24
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Wu T, Wang L, Gao C, Jian C, Liu Y, Fu Z, Shi C. Treg-Derived Extracellular Vesicles: Roles in Diseases and Theranostics. Mol Pharm 2024; 21:2659-2672. [PMID: 38695194 DOI: 10.1021/acs.molpharmaceut.4c00233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2024]
Abstract
Regulatory T cells (Tregs), a subset of CD4+ T cells, are indispensable in maintaining immune self-tolerance and have been utilized in various diseases. Treg-derived extracellular vesicles (Treg-EVs) have been discovered to play an important role in the mechanism of Treg functions. As cell-derived membranous particles, EVs carry multiple bioactive substances that possess tremendous potential for theranostics. Treg-EVs are involved in numerous physiological and pathological processes, carrying proteins and miRNAs inherited from the parental cells. To comprehensively understand the function of Treg-EVs, here we reviewed the classification of Treg-EVs, the active molecules in Treg-EVs, their various applications in diseases, and the existing challenges for Treg-EVs based theranostics. This Review aims to clarify the feasibility and potential of Treg-EVs in diseases and theranostics, facilitating further research and application of Treg-EVs.
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Affiliation(s)
- Tingting Wu
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China
| | - Lulu Wang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China
| | - Chen Gao
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China
| | - Chen Jian
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China
| | - Yajing Liu
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China
| | - Zhiwen Fu
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China
| | - Chen Shi
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, China
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25
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Lee SH, Song SY. Recent Advancement in Diagnosis of Biliary Tract Cancer through Pathological and Molecular Classifications. Cancers (Basel) 2024; 16:1761. [PMID: 38730713 PMCID: PMC11083053 DOI: 10.3390/cancers16091761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 04/24/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Biliary tract cancers (BTCs), including intrahepatic, perihilar, and distal cholangiocarcinomas, as well as gallbladder cancer, are a diverse group of cancers that exhibit unique molecular characteristics in each of their anatomic and pathological subtypes. The pathological classification of BTCs compromises distinct growth patterns, including mass forming, periductal infiltrating, and intraductal growing types, which can be identified through gross examination. The small-duct and large-duct types of intrahepatic cholangiocarcinoma have been recently introduced into the WHO classification. The presentation of typical clinical symptoms, as well as the extensive utilization of radiological, endoscopic, and molecular diagnostic methods, is thoroughly detailed in the description. To overcome the limitations of traditional tissue acquisition methods, new diagnostic modalities are being explored. The treatment landscape is also rapidly evolving owing to the emergence of distinct subgroups with unique molecular alterations and corresponding targeted therapies. Furthermore, we emphasize the crucial aspects of diagnosing BTC in practical clinical settings.
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Affiliation(s)
- Sang-Hoon Lee
- Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Republic of Korea;
| | - Si Young Song
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03772, Republic of Korea
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26
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Wang J, Shi R, Yin Y, Luo H, Cao Y, Lyu Y, Luo H, Zeng X, Wang D. Clinical significance of small extracellular vesicles in cholangiocarcinoma. Front Oncol 2024; 14:1334592. [PMID: 38665948 PMCID: PMC11043544 DOI: 10.3389/fonc.2024.1334592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 03/28/2024] [Indexed: 04/28/2024] Open
Abstract
Cholangiocarcinoma is an aggressive and heterogeneous malignancy originating from the bile duct epithelium. It is associated with poor prognosis and high mortality. The global incidence of cholangiocarcinoma is rising, and there is an urgent need for effective early diagnosis and treatment strategies to reduce the burden of this devastating tumor. Small extracellular vesicles, including exosomes and microparticles, are nanoscale vesicles formed by membranes that are released both normally and pathologically from cells, mediating the intercellular transfer of substances and information. Recent studies have demonstrated the involvement of small extracellular vesicles in numerous biological processes, as well as the proliferation, invasion, and metastasis of tumor cells. The present review summarizes the tumorigenic roles of small extracellular vesicles in the cholangiocarcinoma microenvironment. Owing to their unique composition, accessibility, and stability in biological fluids, small extracellular vesicles have emerged as ideal biomarkers for use in liquid biopsies for diagnosing and outcome prediction of cholangiocarcinoma. Specific tissue tropism, theoretical biocompatibility, low clearance, and strong biological barrier penetration of small extracellular vesicles make them suitable drug carriers for cancer therapy. Furthermore, the potential value of small extracellular vesicle-based therapies for cholangiocarcinoma is also reviewed.
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Affiliation(s)
- Jianjun Wang
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
- National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Ruizi Shi
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Yuan Yin
- National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Hua Luo
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Yuan Cao
- Department of Urology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Yun Lyu
- Departmant of Oncology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Huiwen Luo
- National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Xintao Zeng
- Department of Hepatobiliary Surgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Decai Wang
- National Health Commission (NHC) Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
- Department of Urology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
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27
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Wang R, Ren C, Gao T, Li H, Bo X, Zhu D, Zhang D, Chen H, Zhang Y. SEPDB: a database of secreted proteins. Database (Oxford) 2024; 2024:baae007. [PMID: 38345567 PMCID: PMC10878045 DOI: 10.1093/database/baae007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 12/14/2023] [Accepted: 01/24/2024] [Indexed: 02/15/2024]
Abstract
Detecting changes in the dynamics of secreted proteins in serum has been a challenge for proteomics. Enter secreted protein database (SEPDB), an integrated secretory proteomics database offering human, mouse and rat secretory proteomics datasets collected from serum, exosomes and cell culture media. SEPDB compiles secreted protein information from secreted protein database, UniProt and Human Protein Atlas databases to annotate secreted proteomics data based on protein subcellular localization and disease markers. SEPDB integrates the latest predictive modeling techniques to measure deviations in the distribution of signal peptide structures of secreted proteins, extends signal peptide sequence prediction by excluding transmembrane structural domain proteins and updates the validation analysis pipeline for secreted proteins. To establish tissue-specific profiles, we have also created secreted proteomics datasets associated with different human tissues. In addition, we provide information on heterogeneous receptor network organizational relationships, reflective of the complex functional information inherent in the molecular structures of secreted proteins that serve as ligands. Users can take advantage of the Refreshed Search, Analyze, Browse and Download functions of SEPDB, which is available online at https://sysomics.com/SEPDB/. Database URL: https://sysomics.com/SEPDB/.
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Affiliation(s)
- Ruiqing Wang
- The State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, #5 Dong Dan San Tiao, Beijing 100005, China
- Experimental Center, Shandong University of Traditional Chinese Medicine, Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, #4655 Daxue Road, Changqing District, Jinan, Shandong Province 250355, China
| | - Chao Ren
- Institute of Health Service and Transfusion Medicine, #27 Taiping Road, Haidian District, Beijing 100850, China
| | - Tian Gao
- The State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, #5 Dong Dan San Tiao, Beijing 100005, China
- Experimental Center, Shandong University of Traditional Chinese Medicine, Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, #4655 Daxue Road, Changqing District, Jinan, Shandong Province 250355, China
| | - Hao Li
- Institute of Health Service and Transfusion Medicine, #27 Taiping Road, Haidian District, Beijing 100850, China
| | - Xiaochen Bo
- Institute of Health Service and Transfusion Medicine, #27 Taiping Road, Haidian District, Beijing 100850, China
| | - Dahai Zhu
- The State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, #5 Dong Dan San Tiao, Beijing 100005, China
- Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), #96 South Xingdao Ring Road, Haizhu District, Guangzhou 510005, China
| | - Dan Zhang
- Experimental Center, Shandong University of Traditional Chinese Medicine, Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, #4655 Daxue Road, Changqing District, Jinan, Shandong Province 250355, China
| | - Hebing Chen
- Institute of Health Service and Transfusion Medicine, #27 Taiping Road, Haidian District, Beijing 100850, China
| | - Yong Zhang
- The State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, #5 Dong Dan San Tiao, Beijing 100005, China
- Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), #96 South Xingdao Ring Road, Haizhu District, Guangzhou 510005, China
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28
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Shu L, Li X, Liu Z, Li K, Shi A, Tang Y, Zhao L, Huang L, Zhang Z, Zhang D, Huang S, Lian S, Sheng G, Yan Z, Zhang Z, Xu Y. Bile exosomal miR-182/183-5p increases cholangiocarcinoma stemness and progression by targeting HPGD and increasing PGE2 generation. Hepatology 2024; 79:307-322. [PMID: 37140231 DOI: 10.1097/hep.0000000000000437] [Citation(s) in RCA: 25] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 04/22/2023] [Indexed: 05/05/2023]
Abstract
BACKGROUND AIMS Cholangiocarcinoma (CCA) is a highly lethal malignancy originating from the biliary ducts. Current CCA diagnostic and prognostic assessments cannot satisfy the clinical requirement. Bile detection is rarely performed, and herein, we aim to estimate the clinical significance of bile liquid biopsy by assessing bile exosomal concentrations and components. APPROACH RESULTS Exosomes in bile and sera from CCA, pancreatic cancer, and common bile duct stone were identified and quantified by transmission electronmicroscopy, nanoparticle tracking analysis, and nanoFCM. Exosomal components were assessed by liquid chromatography with tandem mass spectrometry and microRNA sequencing (miRNA-seq). Bile exosomal concentration in different diseases had no significant difference, but miR-182-5p and miR-183-5p were ectopically upregulated in CCA bile exosomes. High miR-182/183-5p in both CCA tissues and bile indicates a poor prognosis. Bile exosomal miR-182/183-5p is secreted by CCA cells and can be absorbed by biliary epithelium or CCA cells. With xenografts in humanized mice, we showed that bile exosomal miR-182/183-5p promotes CCA proliferation, invasion, and epithelial-mesenchymal transition (EMT) by targeting hydroxyprostaglandin dehydrogenase in CCA cells and mast cells (MCs), and increasing prostaglandin E2 generation, which stimulates PTGER1 and increases CCA stemness. In single-cell mRNA-seq, hydroxyprostaglandin dehydrogenase is predominantly expressed in MCs. miR-182/183-5p prompts MC to release VEGF-A release from MC by increasing VEGF-A expression, which facilitates angiogenesis. CONCLUSIONS CCA cells secret exosomal miR-182/183-5p into bile, which targets hydroxyprostaglandin dehydrogenase in CCA cells and MCs and increases prostaglandin E2 and VEGF-A release. Prostaglandin E2 promotes stemness by activating PTGER1. Our results reveal a type of CCA self-driven progression dependent on bile exosomal miR-182/183-5p and MCs, which is a new interplay pattern of CCA and bile.
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Affiliation(s)
- Lizhuang Shu
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Xingyong Li
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Zengli Liu
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- Department of General Surgery, Qilu Hospital (Qingdao), Shandong University, Qingdao, Shandong, China
| | - Kangshuai Li
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Anda Shi
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yongchang Tang
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Liming Zhao
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Lingling Huang
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, Key Laboratory of Chemical Biology(Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Zhiyue Zhang
- NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, Key Laboratory of Chemical Biology(Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Dong Zhang
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Shaohui Huang
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Shuo Lian
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Guoli Sheng
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Zhangdi Yan
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Zongli Zhang
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yunfei Xu
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
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29
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Yu L, Zeng X, Hu X, Wen Q, Chen P. Advances and challenges in clinical applications of tumor cell-derived extracellular vesicles. Colloids Surf B Biointerfaces 2024; 234:113704. [PMID: 38113751 DOI: 10.1016/j.colsurfb.2023.113704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/05/2023] [Accepted: 12/07/2023] [Indexed: 12/21/2023]
Abstract
Extracellular vesicles (EVs) are a class of substances that feature vesicle-like structures. Initially deemed to be "biological waste", recent studies have highlighted the crucial role of EVs in mediating information communication between cells by transporting bioactive components. Specifically, tumor cell-derived extracellular vesicles (TEVs) contain components that can be utilized for disease diagnosis and as vaccines to activate the immune system. Moreover, since TEVs have a phospholipid bilayer shell and can transport exogenous substances, they are being increasingly explored as drug delivery vehicles in anti-tumor therapy. TEVs have proven highly compatible with their corresponding tumor cells, allowing for efficient drug delivery and exerting killing effects on tumor cells through various mechanisms such as domino effects, lysosomal pathways, and inhibition of drug efflux from tumor tissues. Despite these promising developments, challenges remain in the clinical applications of EVs derived from tumor cells. This paper outlines the current advances and limitations in this field, highlighting the potential of TEVs as a powerful tool for combating cancer.
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Affiliation(s)
- Li Yu
- Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Department of Oncology, Jiangsu Cancer Hospital, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210009, China
| | - Xiaonan Zeng
- Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Xiao Hu
- Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Department of Oncology, the Second Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
| | - Qinglian Wen
- Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
| | - Ping Chen
- Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
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30
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Ceccherini E, Michelucci E, Signore G, Coco B, Zari M, Bellini M, Brunetto MR, Cecchettini A, Rocchiccioli S. The Clinical Utility of the Saliva Proteome in Rare Diseases: A Pilot Study for Biomarker Discovery in Primary Sclerosing Cholangitis. J Clin Med 2024; 13:544. [PMID: 38256678 PMCID: PMC10816894 DOI: 10.3390/jcm13020544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/08/2024] [Accepted: 01/16/2024] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory liver disease characterized by biliary strictures and cholestasis. Due to the lack of effective serological indicators for diagnosis and prognosis, in the present study, we examined the potentiality of the saliva proteome to comprehensively screen for novel biomarkers. METHODS Saliva samples of PSC patients and healthy controls were processed and subsequently analyzed using a liquid chromatography-tandem mass spectrometry technique. A bioinformatic approach was applied to detect the differentially expressed proteins, their related biological functions and pathways, and the correlation with the clinical evidence in order to identify a possible marker for the PSC group. RESULTS We identified 25 differentially expressed proteins in PSC patients when compared to the healthy control group. Among them, eight proteins exhibited area under the curve values up to 0.800, suggesting these saliva proteins as good discriminators between the two groups. Multiple positive correlations were also identified between the dysregulated salivary proteins and increased serum alkaline phosphatase levels and the presence of ulcerative colitis. Pathway analysis revealed significant enrichments in the immune system, neutrophil degranulation, and in the interleukine-17 signaling pathway. CONCLUSION We demonstrated the potentiality of saliva as a useful biofluid to obtain a fingerprint of the pathology, suggesting disulfide-isomerase A3 and peroxiredoxin-5 as the better discriminating proteins in PSC patients. Hence, analysis of saliva proteins could become, in future, a useful tool in the screening of patients with suspected PSC.
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Affiliation(s)
- Elisa Ceccherini
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy; (E.M.); (G.S.); (A.C.); (S.R.)
| | - Elena Michelucci
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy; (E.M.); (G.S.); (A.C.); (S.R.)
- Institute of Chemistry of Organometallic Compounds, National Research Council, 56124 Pisa, Italy
| | - Giovanni Signore
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy; (E.M.); (G.S.); (A.C.); (S.R.)
- Biochemistry Unit, Department of Biology, University of Pisa, 56123 Pisa, Italy
| | - Barbara Coco
- Hepatology Unit, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, 56124 Pisa, Italy; (B.C.); (M.R.B.)
| | - Michela Zari
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy; (M.Z.); (M.B.)
| | - Massimo Bellini
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy; (M.Z.); (M.B.)
| | - Maurizia Rossana Brunetto
- Hepatology Unit, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, 56124 Pisa, Italy; (B.C.); (M.R.B.)
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Antonella Cecchettini
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy; (E.M.); (G.S.); (A.C.); (S.R.)
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Silvia Rocchiccioli
- Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy; (E.M.); (G.S.); (A.C.); (S.R.)
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Tian W, Shi D, Zhang Y, Wang H, Tang H, Han Z, Wong CCL, Cui L, Zheng J, Chen Y. Deep proteomic analysis of obstetric antiphospholipid syndrome by DIA-MS of extracellular vesicle enriched fractions. Commun Biol 2024; 7:99. [PMID: 38225453 PMCID: PMC10789860 DOI: 10.1038/s42003-024-05789-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 01/03/2024] [Indexed: 01/17/2024] Open
Abstract
Proteins in the plasma/serum mirror an individual's physiology. Circulating extracellular vesicles (EVs) proteins constitute a large portion of the plasma/serum proteome. Thus, deep and unbiased proteomic analysis of circulating plasma/serum extracellular vesicles holds promise for discovering disease biomarkers as well as revealing disease mechanisms. We established a workflow for simple, deep, and reproducible proteome analysis of both serum large and small EVs enriched fractions by ultracentrifugation plus 4D-data-independent acquisition mass spectrometry (4D-DIA-MS). In our cohort study of obstetric antiphospholipid syndrome (OAPS), 4270 and 3328 proteins were identified from large and small EVs enriched fractions respectively. Both of them revealed known or new pathways related to OAPS. Increased levels of von Willebrand factor (VWF) and insulin receptor (INSR) were identified as candidate biomarkers, which shed light on hypercoagulability and abnormal insulin signaling in disease progression. Our workflow will significantly promote our understanding of plasma/serum-based disease mechanisms and generate new biomarkers.
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Affiliation(s)
- Wenmin Tian
- Department of Biochemistry and Biophysics, Center for Precision Medicine Multi-Omics Research, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
| | - Dongxue Shi
- Department of Biochemistry and Biophysics, Center for Precision Medicine Multi-Omics Research, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
| | - Yinmei Zhang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, P R China
| | - Hongli Wang
- Department of Biochemistry and Biophysics, Center for Precision Medicine Multi-Omics Research, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
| | - Haohao Tang
- Department of Biochemistry and Biophysics, Center for Precision Medicine Multi-Omics Research, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China
| | - Zhongyu Han
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, P R China
| | - Catherine C L Wong
- Department of Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 100730, Beijing, China
- Tsinghua University-Peking University Joint Center for Life Sciences, Peking University, 100084, Beijing, China
| | - Liyan Cui
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, P R China.
| | - Jiajia Zheng
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, P R China.
| | - Yang Chen
- Department of Biochemistry and Biophysics, Center for Precision Medicine Multi-Omics Research, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
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Hánělová K, Raudenská M, Masařík M, Balvan J. Protein cargo in extracellular vesicles as the key mediator in the progression of cancer. Cell Commun Signal 2024; 22:25. [PMID: 38200509 PMCID: PMC10777590 DOI: 10.1186/s12964-023-01408-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 11/24/2023] [Indexed: 01/12/2024] Open
Abstract
Exosomes are small vesicles of endosomal origin that are released by almost all cell types, even those that are pathologically altered. Exosomes widely participate in cell-to-cell communication via transferring cargo, including nucleic acids, proteins, and other metabolites, into recipient cells. Tumour-derived exosomes (TDEs) participate in many important molecular pathways and affect various hallmarks of cancer, including fibroblasts activation, modification of the tumour microenvironment (TME), modulation of immune responses, angiogenesis promotion, setting the pre-metastatic niche, enhancing metastatic potential, and affecting therapy sensitivity and resistance. The unique exosome biogenesis, composition, nontoxicity, and ability to target specific tumour cells bring up their use as promising drug carriers and cancer biomarkers. In this review, we focus on the role of exosomes, with an emphasis on their protein cargo, in the key mechanisms promoting cancer progression. We also briefly summarise the mechanism of exosome biogenesis, its structure, protein composition, and potential as a signalling hub in both normal and pathological conditions. Video Abstract.
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Affiliation(s)
- Klára Hánělová
- Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, CZ-625 00, Czech Republic
| | - Martina Raudenská
- Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, CZ-625 00, Czech Republic
- Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, CZ-625 00, Czech Republic
| | - Michal Masařík
- Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, CZ-625 00, Czech Republic
- Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, CZ-625 00, Czech Republic
- BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, Vestec, CZ-252 50, Czech Republic
| | - Jan Balvan
- Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, CZ-625 00, Czech Republic.
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Zhang N, Shu L, Liu Z, Shi A, Zhao L, Huang S, Sheng G, Yan Z, Song Y, Huang F, Tang Y, Zhang Z. The role of extracellular vesicles in cholangiocarcinoma tumor microenvironment. Front Pharmacol 2024; 14:1336685. [PMID: 38269274 PMCID: PMC10805838 DOI: 10.3389/fphar.2023.1336685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 12/26/2023] [Indexed: 01/26/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor that originates from the biliary system. With restricted treatment options at hand, the challenging aspect of early CCA diagnosis leads to a bleak prognosis. Besides the intrinsic characteristics of tumor cells, the generation and progression of CCA are profoundly influenced by the tumor microenvironment, which engages in intricate interactions with cholangiocarcinoma cells. Of notable significance is the role of extracellular vesicles as key carriers in enabling communication between cancer cells and the tumor microenvironment. This review aims to provide a comprehensive overview of current research examining the interplay between extracellular vesicles and the tumor microenvironment in the context of CCA. Specifically, we will emphasize the significant contributions of extracellular vesicles in molding the CCA microenvironment and explore their potential applications in the diagnosis, prognosis assessment, and therapeutic strategies for this aggressive malignancy.
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Affiliation(s)
- Nuoqi Zhang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Lizhuang Shu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zengli Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
- Department of General Surgery, Qilu Hospital, Shandong University, Qingdao, Shandong, China
| | - Anda Shi
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Liming Zhao
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Shaohui Huang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Guoli Sheng
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhangdi Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yan Song
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Fan Huang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yongchang Tang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zongli Zhang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
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Ihlamur M, Kelleci K, Zengin Y, Allahverdiyev MA, Abamor EŞ. Applications of Exosome Vesicles in Different Cancer Types as Biomarkers. Curr Mol Med 2024; 24:281-297. [PMID: 36941811 DOI: 10.2174/1566524023666230320120419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 12/11/2022] [Accepted: 01/09/2023] [Indexed: 03/23/2023]
Abstract
One of the biggest challenges in the fight against cancer is early detection. Early diagnosis is vital, but there are some barriers such as economic, cultural, and personal factors. Considering the disadvantages of radiological imaging techniques or serological analysis methods used in cancer diagnosis, such as being expensive, requiring expertise, and being time-consuming, there is a need to develop faster, more reliable, and cost-effective diagnostic methods for use in cancer diagnosis. Exosomes, which are responsible for intercellular communication with sizes ranging from 30-120 nm, are naturally produced biological nanoparticles. Thanks to the cargo contents they carry, they are a potential biomarker to be used in the diagnosis of cancer. Exosomes, defined as extracellular vesicles of endosomal origin, are effective in cancer growth, progression, metastasis, and drug resistance, and changes in microenvironmental conditions during tumor development change exosome secretion. Due to their high cellular activity, tumor cells produce much higher exosomes than healthy cells. Therefore, it is known that the number of exosomes in body fluids is significantly rich compared to other cells and can act as a stand-alone diagnostic biomarker. Cancer- derived exosomes have received great attention in recent years for the early detection of cancer and the evaluation of therapeutic response. In this article, the content, properties, and differences of exosomes detected in common types of cancer (lung, liver, pancreas, ovaries, breast, colorectal), which are the leading causes of cancer-related deaths, are reviewed. We also discuss the potential utility of exosome contents as a biomarker for early detection, which is known to be important in targeted cancer therapy.
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Affiliation(s)
- Murat Ihlamur
- Yildiz Technical University, Faculty of Chemistry and Metallurgy, Department of Bioengineering, Istanbul, Turkey
- Biruni University, Vocational School, Department of Electronics and Automation, Istanbul, Turkey
| | - Kübra Kelleci
- Yildiz Technical University, Faculty of Chemistry and Metallurgy, Department of Bioengineering, Istanbul, Turkey
- Beykoz University, Vocational School, Department of Medical Services and Techniques, Istanbul, Turkey
| | - Yağmur Zengin
- Bogazici University, Biomedical Engineering Institute, Department of Biomedical Engineering, Istanbul, Turkey
| | - M Adil Allahverdiyev
- Institute of the V. Akhundov National Scientific Research Medical Prophylactic, Baku, Azerbaijan Republic
| | - Emrah Şefik Abamor
- Yildiz Technical University, Faculty of Chemistry and Metallurgy, Department of Bioengineering, Istanbul, Turkey
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35
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Tsoneva DK, Ivanov MN, Vinciguerra M. Liquid Liver Biopsy for Disease Diagnosis and Prognosis. J Clin Transl Hepatol 2023; 11:1520-1541. [PMID: 38161500 PMCID: PMC10752811 DOI: 10.14218/jcth.2023.00040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 05/24/2023] [Accepted: 06/07/2023] [Indexed: 01/03/2024] Open
Abstract
Liver diseases are a major burden worldwide, the scope of which is expected to further grow in the upcoming years. Clinically relevant liver dysfunction-related blood markers such as alanine aminotransferase and aspartate aminotransferase have limited accuracy. Nowadays, liver biopsy remains the gold standard for several liver-related pathologies, posing a risk of complication due to its invasive nature. Liquid biopsy is a minimally invasive approach, which has shown substantial potential in the diagnosis, prognosis, and monitoring of liver diseases by detecting disease-associated particles such as proteins and RNA molecules in biological fluids. Histones are the core components of the nucleosomes, regulating essential cellular processes, including gene expression and DNA repair. Following cell death or activation of immune cells, histones are released in the extracellular space and can be detected in circulation. Histones are stable in circulation, have a long half-life, and retain their post-translational modifications. Here, we provide an overview of the current research on histone-mediated liquid biopsy methods for liver diseases, with a focus on the most common detection methods.
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Affiliation(s)
- Desislava K. Tsoneva
- Department of Medical Genetics, Medical University of Varna, Varna, Bulgaria
- Department of Stem Cell Biology and Transplantology, Research Institute, Medical University of Varna, Varna, Bulgaria
| | - Martin N. Ivanov
- Department of Stem Cell Biology and Transplantology, Research Institute, Medical University of Varna, Varna, Bulgaria
- Department of Anatomy and Cell Biology, Research Institute, Medical University of Varna, Varna, Bulgaria
| | - Manlio Vinciguerra
- Department of Stem Cell Biology and Transplantology, Research Institute, Medical University of Varna, Varna, Bulgaria
- Faculty of Health, Liverpool John Moores University, Liverpool, United Kingdom
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36
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Abyadeh M, Alikhani M, Mirzaei M, Gupta V, Shekari F, Salekdeh GH. Proteomics provides insights into the theranostic potential of extracellular vesicles. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2023; 138:101-133. [PMID: 38220422 DOI: 10.1016/bs.apcsb.2023.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2024]
Abstract
Extracellular vesicles (EVs) encompass a diverse range of membranous structures derived from cells, including exosomes and microvesicles. These vesicles are present in biological fluids and play vital roles in various physiological and pathological processes. They facilitate intercellular communication by enabling the exchange of proteins, lipids, and genetic material between cells. Understanding the cellular processes that govern EV biology is essential for unraveling their physiological and pathological functions and their potential clinical applications. Despite significant advancements in EV research in recent years, there is still much to learn about these vesicles. The advent of improved mass spectrometry (MS)-based techniques has allowed for a deeper characterization of EV protein composition, providing valuable insights into their roles in different physiological and pathological conditions. In this chapter, we provide an overview of proteomics studies conducted to identify the protein contents of EVs, which contribute to their therapeutic and pathological features. We also provided evidence on the potential of EV proteome contents as biomarkers for early disease diagnosis, progression, and treatment response, as well as factors that influence their composition. Additionally, we discuss the available databases containing information on EV proteome contents, and finally, we highlight the need for further research to pave the way toward their utilization in clinical settings.
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Affiliation(s)
- Morteza Abyadeh
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Mehdi Alikhani
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Mehdi Mirzaei
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, North Ryde, Sydney, NSW, Australia
| | - Vivek Gupta
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, North Ryde, Sydney, NSW, Australia
| | - Faezeh Shekari
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
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Fonseca Teixeira A, Wu S, Luwor R, Zhu HJ. A New Era of Integration between Multiomics and Spatio-Temporal Analysis for the Translation of EMT towards Clinical Applications in Cancer. Cells 2023; 12:2740. [PMID: 38067168 PMCID: PMC10706093 DOI: 10.3390/cells12232740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 11/28/2023] [Accepted: 11/28/2023] [Indexed: 12/18/2023] Open
Abstract
Epithelial-mesenchymal transition (EMT) is crucial to metastasis by increasing cancer cell migration and invasion. At the cellular level, EMT-related morphological and functional changes are well established. At the molecular level, critical signaling pathways able to drive EMT have been described. Yet, the translation of EMT into efficient diagnostic methods and anti-metastatic therapies is still missing. This highlights a gap in our understanding of the precise mechanisms governing EMT. Here, we discuss evidence suggesting that overcoming this limitation requires the integration of multiple omics, a hitherto neglected strategy in the EMT field. More specifically, this work summarizes results that were independently obtained through epigenomics/transcriptomics while comprehensively reviewing the achievements of proteomics in cancer research. Additionally, we prospect gains to be obtained by applying spatio-temporal multiomics in the investigation of EMT-driven metastasis. Along with the development of more sensitive technologies, the integration of currently available omics, and a look at dynamic alterations that regulate EMT at the subcellular level will lead to a deeper understanding of this process. Further, considering the significance of EMT to cancer progression, this integrative strategy may enable the development of new and improved biomarkers and therapeutics capable of increasing the survival and quality of life of cancer patients.
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Affiliation(s)
- Adilson Fonseca Teixeira
- Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, Australia (S.W.); (R.L.)
- Huagene Institute, Kecheng Science and Technology Park, Pukou District, Nanjing 211800, China
| | - Siqi Wu
- Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, Australia (S.W.); (R.L.)
- Huagene Institute, Kecheng Science and Technology Park, Pukou District, Nanjing 211800, China
| | - Rodney Luwor
- Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, Australia (S.W.); (R.L.)
- Huagene Institute, Kecheng Science and Technology Park, Pukou District, Nanjing 211800, China
- Fiona Elsey Cancer Research Institute, Ballarat, VIC 3350, Australia
- Health, Innovation and Transformation Centre, Federation University, Ballarat, VIC 3350, Australia
| | - Hong-Jian Zhu
- Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, Australia (S.W.); (R.L.)
- Huagene Institute, Kecheng Science and Technology Park, Pukou District, Nanjing 211800, China
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Srinivas AN, Suresh D, Kaur S, Kumar DP. The promise of small particles: extracellular vesicles as biomarkers in liver pathology. J Physiol 2023; 601:4953-4971. [PMID: 35708653 DOI: 10.1113/jp283074] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/07/2022] [Indexed: 11/09/2022] Open
Abstract
Extracellular vesicles (EVs) are nanoscopic packages that are heterogeneous and bona fide players in hepatic physiology and pathology as they are involved in intercellular communication. EVs carrying bioactive cargoes rich in lipids, proteins or nucleic acids are implicated in the onset and progression of liver diseases. Liver pathology using liver biopsy has been assessed for several intricate conditions such as viral hepatitis, alcoholic and non-alcoholic fatty liver disease, hepatic malignancies and drug-induced liver injury. The lacunae, however, lie in early diagnosis and timely treatment of the above conditions, underscoring the need for non-invasive, accurate diagnostic tools that could replace the gold standard method of tissue biopsy. In this regard, EVs have emerged as promising candidates that could serve as potential biomarkers. In the last two decades, EVs, owing to their multifaceted charm in bringing out cell-free therapeutic responses and the ability of their cargoes to be applied to novel biomarkers, have drawn the great attention of researchers with the advancement and clinical application of liquid biopsy. In this review, we recapitulate the role of EVs and provide insights into the promising role of these small packages as biomarkers in liver pathology.
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Affiliation(s)
- Akshatha N Srinivas
- Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India
| | - Diwakar Suresh
- Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India
| | - Savneet Kaur
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Divya P Kumar
- Department of Biochemistry, CEMR, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India
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Trifylli EM, Kriebardis AG, Koustas E, Papadopoulos N, Vasileiadi S, Fortis SP, Tzounakas VL, Anastasiadi AT, Sarantis P, Papageorgiou EG, Tsagarakis A, Aloizos G, Manolakopoulos S, Deutsch M. The Arising Role of Extracellular Vesicles in Cholangiocarcinoma: A Rundown of the Current Knowledge Regarding Diagnostic and Therapeutic Approaches. Int J Mol Sci 2023; 24:15563. [PMID: 37958547 PMCID: PMC10649642 DOI: 10.3390/ijms242115563] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 10/21/2023] [Accepted: 10/23/2023] [Indexed: 11/15/2023] Open
Abstract
Cholangiocarcinomas (CCAs) constitute a heterogeneous group of highly malignant epithelial tumors arising from the biliary tree. This cluster of malignant tumors includes three distinct entities, the intrahepatic, perihilar, and distal CCAs, which are characterized by different epidemiological and molecular backgrounds, as well as prognosis and therapeutic approaches. The higher incidence of CCA over the last decades, the late diagnostic time that contributes to a high mortality and poor prognosis, as well as its chemoresistance, intensified the efforts of the scientific community for the development of novel diagnostic tools and therapeutic approaches. Extracellular vesicles (EVs) comprise highly heterogenic, multi-sized, membrane-enclosed nanostructures that are secreted by a large variety of cells via different routes of biogenesis. Their role in intercellular communication via their cargo that potentially contributes to disease development and progression, as well as their prospect as diagnostic biomarkers and therapeutic tools, has become the focus of interest of several current studies for several diseases, including CCA. The aim of this review is to give a rundown of the current knowledge regarding the emerging role of EVs in cholangiocarcinogenesis and their future perspectives as diagnostic and therapeutic tools.
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Affiliation(s)
- Eleni-Myrto Trifylli
- Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. Spyridonos Str., 12243 Egaleo, Greece; (E.-M.T.); (S.P.F.); (E.G.P.)
- First Department of Internal Medicine, 417 Army Share Fund Hospital, 11521 Athens, Greece;
- 2nd Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, Vasilissis Sofias Avenue Str., 11527 Athens, Greece; (S.V.); (S.M.); (M.D.)
| | - Anastasios G. Kriebardis
- Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. Spyridonos Str., 12243 Egaleo, Greece; (E.-M.T.); (S.P.F.); (E.G.P.)
| | - Evangelos Koustas
- Oncology Department, General Hospital Evangelismos, 10676 Athens, Greece;
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Nikolaos Papadopoulos
- Second Department of Internal Medicine, 401 General Military Hospital, 115 27 Athens, Greece;
| | - Sofia Vasileiadi
- 2nd Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, Vasilissis Sofias Avenue Str., 11527 Athens, Greece; (S.V.); (S.M.); (M.D.)
| | - Sotirios P. Fortis
- Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. Spyridonos Str., 12243 Egaleo, Greece; (E.-M.T.); (S.P.F.); (E.G.P.)
| | - Vassilis L. Tzounakas
- Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece; (V.L.T.); (A.T.A.)
| | - Alkmini T. Anastasiadi
- Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece; (V.L.T.); (A.T.A.)
| | - Panagiotis Sarantis
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Effie G. Papageorgiou
- Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. Spyridonos Str., 12243 Egaleo, Greece; (E.-M.T.); (S.P.F.); (E.G.P.)
| | - Ariadne Tsagarakis
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA;
| | - Georgios Aloizos
- First Department of Internal Medicine, 417 Army Share Fund Hospital, 11521 Athens, Greece;
| | - Spilios Manolakopoulos
- 2nd Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, Vasilissis Sofias Avenue Str., 11527 Athens, Greece; (S.V.); (S.M.); (M.D.)
| | - Melanie Deutsch
- 2nd Academic Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, Vasilissis Sofias Avenue Str., 11527 Athens, Greece; (S.V.); (S.M.); (M.D.)
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Liu M, Lai Z, Yuan X, Jin Q, Shen H, Rao D, Huang D. Role of exosomes in the development, diagnosis, prognosis and treatment of hepatocellular carcinoma. Mol Med 2023; 29:136. [PMID: 37848835 PMCID: PMC10580543 DOI: 10.1186/s10020-023-00731-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 09/17/2023] [Indexed: 10/19/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is characterized by occult onset resulting in most patients being diagnosed at advanced stages and with poor prognosis. Exosomes are nanoscale vesicles with a lipid bilayer envelope released by various cells under physiological and pathological conditions, which play an important role in the biological information transfer between cells. There is growing evidence that HCC cell-derived exosomes may contribute to the establishment of a favorable microenvironment that supports cancer cell proliferation, invasion, and metastasis. These exosomes not only provide a versatile platform for diagnosis but also serve as a vehicle for drug delivery. In this paper, we review the role of exosomes involved in the proliferation, migration, and metastasis of HCC and describe their application in HCC diagnosis and treatment. We also discuss the prospects of exosome application in HCC and the research challenges.
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Affiliation(s)
- Meijin Liu
- Ganzhou Jingkai District People's Hospital, Ganzhou, China
| | - Zhonghong Lai
- Department of Traumatology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Xiaoying Yuan
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Qing Jin
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Haibin Shen
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Dingyu Rao
- Department of Cardiothoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
| | - Defa Huang
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
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Catanzaro E, Gringeri E, Burra P, Gambato M. Primary Sclerosing Cholangitis-Associated Cholangiocarcinoma: From Pathogenesis to Diagnostic and Surveillance Strategies. Cancers (Basel) 2023; 15:4947. [PMID: 37894314 PMCID: PMC10604939 DOI: 10.3390/cancers15204947] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/09/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Cholangiocarcinoma (CCA) is the most common malignancy in patients with primary sclerosing cholangitis (PSC), accounting for 2-8% of cases and being the leading cause of death in these patients. The majority of PSC-associated CCAs (PSC-CCA) develop within the first few years after PSC diagnosis. Older age and male sex, as well as concomitant inflammatory bowel disease (IBD) or high-grade biliary stenosis, are some of the most relevant risk factors. A complex combination of molecular mechanisms involving inflammatory pathways, direct cytopathic damage, and epigenetic and genetic alterations are involved in cholangiocytes carcinogenesis. The insidious clinical presentation makes early detection difficult, and the integration of biochemical, radiological, and histological features does not always lead to a definitive diagnosis of PSC-CCA. Surveillance is mandatory, but current guideline strategies failed to improve early detection and consequently a higher patient survival rate. MicroRNAs (miRNAs), gene methylation, proteomic and metabolomic profile, and extracellular vesicle components are some of the novel biomarkers recently applied in PSC-CCA detection with promising results. The integration of these new molecular approaches in PSC diagnosis and monitoring could contribute to new diagnostic and surveillance strategies.
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Affiliation(s)
- Elisa Catanzaro
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Center, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Patrizia Burra
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
| | - Martina Gambato
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy
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Hatia RI, Eluri M, Hawk ET, Shalaby A, Karatas E, Shalaby A, Abdelhakeem A, Abdel-Wahab R, Chang P, Rashid A, Jalal PK, Amos CI, Han Y, Armaghany T, Shroff RT, Li D, Javle M, Hassan MM. Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma. Cancer Epidemiol Biomarkers Prev 2023; 32:1338-1347. [PMID: 37540502 DOI: 10.1158/1055-9965.epi-23-0388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/14/2023] [Accepted: 08/01/2023] [Indexed: 08/05/2023] Open
Abstract
BACKGROUND It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States. METHODS We conducted a case-control study of 121 patients with ECC and 308 patients with ICC treated at MD Anderson Cancer Center between May 2014 and March 2020, compared with 1,061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted OR (AOR) and 95% confidence interval (CI) for each risk factor. RESULTS Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20-40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P < 0.001; 6.1 months for ICC, P = 0.001; 8.2 months for ECC, P = 0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95% CI) were 1.11 (1.06-1.48) and 1.32 (1.01-2.00) for ICC and ECC, respectively. CONCLUSIONS In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals. IMPACT The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.
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Affiliation(s)
- Rikita I Hatia
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Madhulika Eluri
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ernest T Hawk
- Division of Cancer Prevention & Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Akram Shalaby
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio
| | - Elif Karatas
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Ahmed Shalaby
- Department of Radiation Oncology, Robert Wood Johnson University Hospital, New Brunswick, New Jersey
| | - Ahmed Abdelhakeem
- Department of Internal Medicine, Baptist Hospital of Southeast Texas, Beaumont, Texas
| | - Reham Abdel-Wahab
- Department of Melanoma Medicine Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
- Clinical Oncology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Ping Chang
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Asif Rashid
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Prasun K Jalal
- Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas
| | - Christopher I Amos
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas
| | - Younghun Han
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas
| | - Tannaz Armaghany
- Division of Hematology & Oncology, Baylor College of Medicine, Houston, Texas
| | - Rachna T Shroff
- Division of Hematology/Oncology, University of Arizona Cancer Center, Tucson, Arizona
| | - Donghui Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Manal M Hassan
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Anastasi F, Botto A, Immordino B, Giovannetti E, McDonnell LA. Proteomics analysis of circulating small extracellular vesicles: Focus on the contribution of EVs to tumor metabolism. Cytokine Growth Factor Rev 2023; 73:3-19. [PMID: 37652834 DOI: 10.1016/j.cytogfr.2023.08.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 08/16/2023] [Indexed: 09/02/2023]
Abstract
The term small extracellular vesicle (sEV) is a comprehensive term that includes any type of cell-derived, membrane-delimited particle that has a diameter < 200 nm, and which includes exosomes and smaller microvesicles. sEVs transfer bioactive molecules between cells and are crucial for cellular homeostasis and particularly during tumor development, where sEVs provide important contributions to the formation of the premetastic niche and to their altered metabolism. sEVs are thus legitimate targets for intervention and have also gained increasing interest as an easily accessible source of biomarkers because they can be rapidly isolated from serum/plasma and their molecular cargo provides information on their cell-of origin. To target sEVs that are specific for a given cell/disease it is essential to identify EV surface proteins that are characteristic of that cell/disease. Mass-spectrometry based proteomics is widely used for the identification and quantification of sEV proteins. The methods used for isolating the sEVs, preparing the sEV sample for proteomics analysis, and mass spectrometry analysis, can have a strong influence on the results and requires careful consideration. This review provides an overview of the approaches used for sEV proteomics and discusses the inherent compromises regarding EV purity versus depth of coverage. Additionally, it discusses the practical applications of the methods to unravel the involvement of sEVs in regulating the metabolism of pancreatic ductal adenocarcinoma (PDAC). The metabolic reprogramming in PDAC includes enhanced glycolysis, elevated glutamine metabolism, alterations in lipid metabolism, mitochondrial dysfunction and hypoxia, all of which are crucial in promoting tumor cell growth. A thorough understanding of these metabolic adaptations is imperative for the development of targeted therapies to exploit PDAC's vulnerabilities.
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Affiliation(s)
- Federica Anastasi
- Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, PI, Italy; National Enterprise for NanoScience and NanoTechnology, Scuola Normale Superiore, Pisa, Italy; BarcelonaBeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain
| | - Asia Botto
- Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, PI, Italy; Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Benoit Immordino
- Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, PI, Italy; Scuola Superiore Sant'Anna, Pisa, Italy
| | - Elisa Giovannetti
- Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, PI, Italy; Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Vrije Universiteit, Amsterdam, the Netherlands
| | - Liam A McDonnell
- Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, PI, Italy.
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Gao M, Du Z, Dong Q, Su S, Tian L. DAP1 regulates osteoblast autophagy via the ATG16L1-LC3 axis in Graves' disease-induced osteoporosis. J Orthop Surg Res 2023; 18:711. [PMID: 37735431 PMCID: PMC10512661 DOI: 10.1186/s13018-023-04171-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 09/07/2023] [Indexed: 09/23/2023] Open
Abstract
OBJECTIVE This study aimed to uncover a critical protein and its mechanisms in modulating autophagy in Graves' disease (GD)-induced osteoporosis (OP). METHODS We discovered the target protein, death-associated protein 1 (DAP1), using bone proteomics analysis. Furthermore, genetic overexpression and knockdown (KD) of DAP1 in bone and MC3T3-E1 cells revealed DAP1 effects on autophagy and osteogenic markers, and autophagic vacuoles in cells were detected using transmission electron microscopy and the microtubule-associated protein 1 light chain 3 alpha (MAP1LC3/LC3) dual fluorescence system. An autophagy polymerase chain reaction (PCR) array kit was used to identify the key molecules associated with DAP1-regulated autophagy. RESULTS DAP1 levels were significantly higher in the bone tissue of GD mice and MC3T3-E1 cells treated with triiodothyronine (T3). DAP1 overexpression reduced LC3 lipidation, autophagic vacuoles, RUNX family transcription factor 2 (RUNX2), and osteocalcin (OCN) expression in MC3T3-E1 cells, whereas DAP1 KD reversed these changes. In vivo experiments revealed that GD mice with DAP1 KD had greater bone mass than control mice. DAP1-overexpressing (OE) cells had lower levels of phosphorylated autophagy-related 16-like 1 (ATG16L1) and LC3 lipidation, whereas DAP1-KD cells had higher levels. CONCLUSIONS DAP1 was found to be a critical regulator of autophagy homeostasis in GD mouse bone tissue and T3-treated osteoblasts because it negatively regulated autophagy and osteogenesis in osteoblasts via the ATG16L1-LC3 axis.
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Affiliation(s)
- Mingdong Gao
- The First School of Clinical Medical, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department Pediatrics, Gansu Provincial Hospital, Lanzhou, 730030, Gansu, China
- Clinical Research Center for Metabolic Diseases, Lanzhou, 730030, Gansu, China
| | - Zouxi Du
- The First School of Clinical Medical, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Qianqian Dong
- The First School of Clinical Medical, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Shan Su
- The First School of Clinical Medical, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Limin Tian
- The First School of Clinical Medical, Lanzhou University, Lanzhou, 730030, Gansu, China.
- Clinical Research Center for Metabolic Diseases, Lanzhou, 730030, Gansu, China.
- Department of Endocrinology, Gansu Provincial Hospital, No. 204 West Donggang Road, Lanzhou, 730030, Gansu, China.
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Zeng Y, Hu S, Luo Y, He K. Exosome Cargos as Biomarkers for Diagnosis and Prognosis of Hepatocellular Carcinoma. Pharmaceutics 2023; 15:2365. [PMID: 37765333 PMCID: PMC10537613 DOI: 10.3390/pharmaceutics15092365] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 09/14/2023] [Accepted: 09/18/2023] [Indexed: 09/29/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Due to the insidiousness of HCC onset and the lack of specific early-stage markers, the early diagnosis and treatment of HCC are still unsatisfactory, leading to a poor prognosis. Exosomes are a type of extracellular vesicle containing various components, which play an essential part in the development, progression, and metastasis of HCC. A large number of studies have demonstrated that exosomes could serve as novel biomarkers for the diagnosis of HCC. These diagnostic components mainly include proteins, microRNAs, long noncoding RNAs, and circular RNAs. The exosome biomarkers showed high sensitivity and high specificity in distinguishing HCC from health controls and other liver diseases, such as chronic HBV and liver cirrhosis. The expression of these biomarkers also exhibits correlations with various clinical factors such as tumor size, TMN stage, overall survival, and recurrence rate. In this review, we summarize the function of exosomes in the development of HCC and highlight their application as HCC biomarkers for diagnosis and prognosis prediction.
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Affiliation(s)
- Yulai Zeng
- Department of Liver Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, China; (Y.Z.); (S.H.)
- Shanghai Engineering Research Center of Transplantation and Immunology, Shanghai 200127, China
- Shanghai Institute of Transplantation, Shanghai 200127, China
| | - Shuyu Hu
- Department of Liver Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, China; (Y.Z.); (S.H.)
- Shanghai Engineering Research Center of Transplantation and Immunology, Shanghai 200127, China
- Shanghai Institute of Transplantation, Shanghai 200127, China
| | - Yi Luo
- Department of Liver Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, China; (Y.Z.); (S.H.)
- Shanghai Engineering Research Center of Transplantation and Immunology, Shanghai 200127, China
- Shanghai Institute of Transplantation, Shanghai 200127, China
| | - Kang He
- Department of Liver Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai 200127, China; (Y.Z.); (S.H.)
- Shanghai Engineering Research Center of Transplantation and Immunology, Shanghai 200127, China
- Shanghai Institute of Transplantation, Shanghai 200127, China
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Yan R, Chen H, Selaru FM. Extracellular Vesicles in Hepatocellular Carcinoma: Progress and Challenges in the Translation from the Laboratory to Clinic. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1599. [PMID: 37763719 PMCID: PMC10534795 DOI: 10.3390/medicina59091599] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 08/27/2023] [Accepted: 08/31/2023] [Indexed: 09/29/2023]
Abstract
Extracellular vesicles (EVs) play critical roles in intercellular communication by transporting bioactive cargo to recipient cells. EVs have been implicated in a range of physiological and pathological processes, including tumor progression, metastasis, immune modulation, and drug resistance. The objective of this review is to present a thorough overview of recent studies focusing on EVs in hepatocellular carcinoma (HCC), with an emphasis on their potential utility as diagnostic biomarkers as well as therapeutic agents. Initially, we explore the utility of EVs as diagnostic biomarkers for HCC, followed by a discussion of their potential as carriers of therapeutic payloads. Additionally, we delve into the emerging field of therapeutic EVs for modulating tumor immune responses. Through this review, our ultimate aim is to provide a comprehensive understanding of the opportunities and challenges in the clinical translation of EV research in the domain of HCC.
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Affiliation(s)
- Rong Yan
- Department of Surgical Oncology, the First Affiliated Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710061, China
| | - Haiming Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA;
| | - Florin M. Selaru
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA;
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21224, USA
- The Institute for Nanobiotechnology, The Johns Hopkins University, Baltimore, MD 21231, USA
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Gao L, Lin Y, Yue P, Li S, Zhang Y, Mi N, Bai M, Fu W, Xia Z, Jiang N, Cao J, Yang M, Ma Y, Zhang F, Zhang C, Leung JW, He S, Yuan J, Meng W, Li X. Identification of a novel bile marker clusterin and a public online prediction platform based on deep learning for cholangiocarcinoma. BMC Med 2023; 21:294. [PMID: 37553571 PMCID: PMC10408060 DOI: 10.1186/s12916-023-02990-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 07/20/2023] [Indexed: 08/10/2023] Open
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor, and its diagnosis is still a challenge. This study aimed to identify a novel bile marker for CCA diagnosis based on proteomics and establish a diagnostic model with deep learning. METHODS A total of 644 subjects (236 CCA and 408 non-CCA) from two independent centers were divided into discovery, cross-validation, and external validation sets for the study. Candidate bile markers were identified by three proteomics data and validated on 635 clinical humoral specimens and 121 tissue specimens. A diagnostic multi-analyte model containing bile and serum biomarkers was established in cross-validation set by deep learning and validated in an independent external cohort. RESULTS The results of proteomics analysis and clinical specimen verification showed that bile clusterin (CLU) was significantly higher in CCA body fluids. Based on 376 subjects in the cross-validation set, ROC analysis indicated that bile CLU had a satisfactory diagnostic power (AUC: 0.852, sensitivity: 73.6%, specificity: 90.1%). Building on bile CLU and 63 serum markers, deep learning established a diagnostic model incorporating seven factors (CLU, CA19-9, IBIL, GGT, LDL-C, TG, and TBA), which showed a high diagnostic utility (AUC: 0.947, sensitivity: 90.3%, specificity: 84.9%). External validation in an independent cohort (n = 259) resulted in a similar accuracy for the detection of CCA. Finally, for the convenience of operation, a user-friendly prediction platform was built online for CCA. CONCLUSIONS This is the largest and most comprehensive study combining bile and serum biomarkers to differentiate CCA. This diagnostic model may potentially be used to detect CCA.
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Affiliation(s)
- Long Gao
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Yanyan Lin
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China
- Gansu Province Key Laboratory of Biological Therapy and Regenerative Medicine Transformation, Lanzhou, 730030, Gansu, China
| | - Ping Yue
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China
- Gansu Province Key Laboratory of Biological Therapy and Regenerative Medicine Transformation, Lanzhou, 730030, Gansu, China
| | - Shuyan Li
- School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Yong Zhang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China
- Gansu Province Key Laboratory of Biological Therapy and Regenerative Medicine Transformation, Lanzhou, 730030, Gansu, China
| | - Ningning Mi
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Mingzhen Bai
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Wenkang Fu
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Zhili Xia
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Ningzu Jiang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Jie Cao
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Man Yang
- Clinical Research Center, Big Data Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, Guangdong, China
| | - Yanni Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Fanxiang Zhang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Chao Zhang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Joseph W Leung
- Division of Gastroenterology, UC Davis Medical Center and Sacramento VA Medical Center, Sacramento, CA, 95817, USA
| | - Shun He
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Jinqiu Yuan
- Clinical Research Center, Big Data Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, Guangdong, China.
| | - Wenbo Meng
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China.
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China.
- Gansu Province Key Laboratory of Biological Therapy and Regenerative Medicine Transformation, Lanzhou, 730030, Gansu, China.
| | - Xun Li
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, Gansu, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730030, Gansu, China
- Gansu Province Key Laboratory of Biological Therapy and Regenerative Medicine Transformation, Lanzhou, 730030, Gansu, China
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Lapitz A, Azkargorta M, Milkiewicz P, Olaizola P, Zhuravleva E, Grimsrud MM, Schramm C, Arbelaiz A, O'Rourke CJ, La Casta A, Milkiewicz M, Pastor T, Vesterhus M, Jimenez-Agüero R, Dill MT, Lamarca A, Valle JW, Macias RIR, Izquierdo-Sanchez L, Pérez Castaño Y, Caballero-Camino FJ, Riaño I, Krawczyk M, Ibarra C, Bustamante J, Nova-Camacho LM, Falcon-Perez JM, Elortza F, Perugorria MJ, Andersen JB, Bujanda L, Karlsen TH, Folseraas T, Rodrigues PM, Banales JM. Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma. J Hepatol 2023; 79:93-108. [PMID: 36868481 PMCID: PMC10292605 DOI: 10.1016/j.jhep.2023.02.027] [Citation(s) in RCA: 90] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 02/09/2023] [Accepted: 02/15/2023] [Indexed: 03/05/2023]
Abstract
BACKGROUND & AIMS Cholangiocarcinoma (CCA), heterogeneous biliary tumours with dismal prognosis, lacks accurate early diagnostic methods especially important for individuals at high-risk (i.e. those with primary sclerosing cholangitis [PSC]). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs). METHODS EVs from patients with isolated PSC (n = 45), concomitant PSC-CCA (n = 44), PSC who developed CCA during follow-up (PSC to CCA; n = 25), CCAs from non-PSC aetiology (n = 56), and hepatocellular carcinoma (n = 34) and healthy individuals (n = 56) were characterised by mass spectrometry. Diagnostic biomarkers for PSC-CCA, non-PSC CCA, or CCAs regardless of aetiology (Pan-CCAs) were defined and validated by ELISA. Their expression was evaluated in CCA tumours at a single-cell level. Prognostic EV biomarkers for CCA were investigated. RESULTS High-throughput proteomics of EVs identified diagnostic biomarkers for PSC-CCA, non-PSC CCA, or Pan-CCA, and for the differential diagnosis of intrahepatic CCA and hepatocellular carcinoma, which were cross-validated by ELISA using total serum. Machine learning-based algorithms disclosed CRP/FIBRINOGEN/FRIL for the diagnosis of PSC-CCA (local disease [LD]) vs. isolated PSC (AUC = 0.947; odds ratio [OR] =36.9) and, combined with carbohydrate antigen 19-9, overpowers carbohydrate antigen 19-9 alone. CRP/PIGR/VWF allowed the diagnosis of LD non-PSC CCAs vs. healthy individuals (AUC = 0.992; OR = 387.5). It is noteworthy that CRP/FRIL accurately diagnosed LD Pan-CCA (AUC = 0.941; OR = 89.4). Levels of CRP/FIBRINOGEN/FRIL/PIGR showed predictive capacity for CCA development in PSC before clinical evidence of malignancy. Multi-organ transcriptomic analysis revealed that serum EV biomarkers were mostly expressed in hepatobiliary tissues, and single-cell RNA sequencing and immunofluorescence analysis of CCA tumours showed their presence mainly in malignant cholangiocytes. Multivariable analysis unveiled EV prognostic biomarkers, with COMP/GNAI2/CFAI and ACTN1/MYCT1/PF4V associated negatively and positively with patients' survival, respectively. CONCLUSIONS Serum EVs contain protein biomarkers for the prediction, early diagnosis, and prognostication of CCA that are detectable using total serum, representing a tumour cell-derived liquid biopsy tool for personalised medicine. IMPACT AND IMPLICATIONS The accuracy of current imaging tests and circulating tumour biomarkers for cholangiocarcinoma (CCA) diagnosis is far from satisfactory. Most CCAs are considered sporadic, although up to 20% of patients with primary sclerosing cholangitis (PSC) develop CCA during their lifetime, constituting a major cause of PSC-related death. This international study has proposed protein-based and aetiology-related logistic models with predictive, diagnostic, or prognostic capacities by combining two to four circulating protein biomarkers, moving a step forward into personalised medicine. These novel liquid biopsy tools may allow the (i) easy and non-invasive diagnosis of sporadic CCAs, (ii) identification of patients with PSC with higher risk for CCA development, (iii) establishment of cost-effective surveillance programmes for the early detection of CCA in high-risk populations (e.g. PSC), and (iv) prognostic stratification of patients with CCA, which, altogether, may increase the number of cases eligible for potentially curative options or to receive more successful treatments, decreasing CCA-related mortality.
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Affiliation(s)
- Ainhoa Lapitz
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Mikel Azkargorta
- Proteomics Platform, CIC BioGUNE, Basque Research and Technology Alliance (BRTA), ProteoRed ISCIII, Bizkaia Science and Technology Park, Derio, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII, Madrid, Spain
| | - Piotr Milkiewicz
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland; Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland
| | - Paula Olaizola
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII, Madrid, Spain
| | - Ekaterina Zhuravleva
- Biotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Marit M Grimsrud
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Christoph Schramm
- European Reference Network Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany; 1st Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Ander Arbelaiz
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Colm J O'Rourke
- Biotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Adelaida La Casta
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Malgorzata Milkiewicz
- Department of Medical Biology, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Tania Pastor
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Mette Vesterhus
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Raul Jimenez-Agüero
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Michael T Dill
- Department of Gastroenterology, Infectious Diseases and Intoxication, Heidelberg University Hospital, Heidelberg, Germany; Experimental Hepatology, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust/Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Juan W Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust/Division of Cancer Sciences, University of Manchester, Manchester, UK
| | - Rocio I R Macias
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII, Madrid, Spain; Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain
| | - Laura Izquierdo-Sanchez
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII, Madrid, Spain
| | - Ylenia Pérez Castaño
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; Osakidetza Basque Health Service, Bidasoa IHO, Bidasoa Hospital, Department of Digestive System, Irun, Spain
| | - Francisco Javier Caballero-Camino
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Ioana Riaño
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; Clinical Research Unit, Spanish Clinical Research Network (SCReN) - ISCIII, Biodonostia Health Research Institute, San Sebastián, Spain
| | - Marcin Krawczyk
- Department of Medicine II, Saarland University Medical Centre, Saarland University, Homburg, Germany
| | - Cesar Ibarra
- Osakidetza Basque Health Service, Ezkerraldea-Enkarterri-Cruces IHO, Cruces University Hospital, Barakaldo, Spain
| | - Javier Bustamante
- Osakidetza Basque Health Service, Ezkerraldea-Enkarterri-Cruces IHO, Cruces University Hospital, Barakaldo, Spain
| | - Luiz M Nova-Camacho
- Osakidetza Basque Health Service, Donostialdea IHO, Donostia University Hospital, Department of Pathology, San Sebastian, Spain
| | - Juan M Falcon-Perez
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII, Madrid, Spain; Center for Cooperative Research in Biosciences (CIC BioGUNE), Basque Research and Technology Alliance (BRTA), Exosomes Laboratory, Derio, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain
| | - Felix Elortza
- Proteomics Platform, CIC BioGUNE, Basque Research and Technology Alliance (BRTA), ProteoRed ISCIII, Bizkaia Science and Technology Park, Derio, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII, Madrid, Spain
| | - Maria J Perugorria
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII, Madrid, Spain; Department of Medicine, Faculty of Medicine and Nursing, University of the Basque Country, UPV/EHU, Leioa, Spain
| | - Jesper B Andersen
- Biotech Research and Innovation Centre, Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Luis Bujanda
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII, Madrid, Spain; Department of Medicine, Faculty of Medicine and Nursing, University of the Basque Country, UPV/EHU, Leioa, Spain
| | - Tom H Karlsen
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Trine Folseraas
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Pedro M Rodrigues
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII, Madrid, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
| | - Jesus M Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain; National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), ISCIII, Madrid, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain; Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
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Mishra A, Bharti PS, Rani N, Nikolajeff F, Kumar S. A tale of exosomes and their implication in cancer. Biochim Biophys Acta Rev Cancer 2023; 1878:188908. [PMID: 37172650 DOI: 10.1016/j.bbcan.2023.188908] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 05/01/2023] [Accepted: 05/05/2023] [Indexed: 05/15/2023]
Abstract
Cancer is a cause of high deaths worldwide and also a huge burden for the health system. Cancer cells have unique properties such as a high rate of proliferation, self-renewal, metastasis, and treatment resistance, therefore, the development of novel diagnoses of cancers is a tedious task. Exosomes are secreted by virtually all cell types and have the ability to carry a multitude of biomolecules crucial for intercellular communication, hence, contributing a crucial part in the onset and spread of cancer. These exosomal components can be utilized in the development of markers for diagnostic and prognostic purposes for various cancers. This review emphasized primarily the following topics: exosomes structure and functions, isolation and characterization strategies of exosomes, the role of exosomal contents in cancer with a focus in particular on noncoding RNA and protein, exosomes, and the cancer microenvironment interactions, cancer stem cells, and tumor diagnosis and prognosis based on exosomes.
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Affiliation(s)
- Abhay Mishra
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Prahalad Singh Bharti
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Neerja Rani
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Fredrik Nikolajeff
- Department of Health, Education, and Technology, Lulea University of Technology, 97187, Sweden
| | - Saroj Kumar
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India; Department of Health, Education, and Technology, Lulea University of Technology, 97187, Sweden.
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Mahmoodpour M, Kiasari BA, Karimi M, Abroshan A, Shamshirian D, Hosseinalizadeh H, Delavari A, Mirzei H. Paper-based biosensors as point-of-care diagnostic devices for the detection of cancers: a review of innovative techniques and clinical applications. Front Oncol 2023; 13:1131435. [PMID: 37456253 PMCID: PMC10348714 DOI: 10.3389/fonc.2023.1131435] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 06/01/2023] [Indexed: 07/18/2023] Open
Abstract
The development and rapid progression of cancer are major social problems. Medical diagnostic techniques and smooth clinical care of cancer are new necessities that must be supported by innovative diagnostic methods and technologies. Current molecular diagnostic tools based on the detection of blood protein markers are the most common tools for cancer diagnosis. Biosensors have already proven to be a cost-effective and accessible diagnostic tool that can be used where conventional laboratory methods are not readily available. Paper-based biosensors offer a new look at the world of analytical techniques by overcoming limitations through the creation of a simple device with significant advantages such as adaptability, biocompatibility, biodegradability, ease of use, large surface-to-volume ratio, and cost-effectiveness. In this review, we covered the characteristics of exosomes and their role in tumor growth and clinical diagnosis, followed by a discussion of various paper-based biosensors for exosome detection, such as dipsticks, lateral flow assays (LFA), and microfluidic paper-based devices (µPADs). We also discussed the various clinical studies on paper-based biosensors for exosome detection.
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Affiliation(s)
- Mehrdad Mahmoodpour
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Bahman Abedi Kiasari
- Virology Department, Faculty of Veterinary, The University of Tehran, Tehran, Iran
| | - Merat Karimi
- Institute of Nanoscience and Nanotechnology, University of Kashan, Kashan, Iran
| | - Arezou Abroshan
- Student Research Committee, Faculty of Veterinary Medicine, Shahid Bahonar University, Kerman, Iran
| | - Danial Shamshirian
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Hosseinalizadeh
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Alireza Delavari
- Student's Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamed Mirzei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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