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Ellakwa DES, Abdelmalek MA, Mostafa MM, Ellakwa TE, Wadan AHS. MircoRNAs predict and modulate responses to chemotherapy in leukemic patients. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:6221-6238. [PMID: 39808312 DOI: 10.1007/s00210-024-03675-7] [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: 10/11/2024] [Accepted: 11/24/2024] [Indexed: 01/16/2025]
Abstract
Leukemia covers a broad category of cancer malignancies that specifically affect bone marrow and blood cells. While different kinds of leukemia have been identified, effective treatments are still lacking for most forms, and even those treatments considered effective can lead to relapses. MicroRNAs, or miRNAs, are short endogenous non-coding single-stranded RNAs that help control the epigenetics of gene expression. Recently, a literature review proposed that miRNAs provided promising therapeutic targets for patients diagnosed with leukemia. Due to genetic abnormalities occurring during the maturation of white blood cells, studies commonly observed uncontrolled replication and decreased cell death, compared to healthy cells. This results in the activation of oncogenes, deactivation of tumor suppressor genes, and disruption of normal cellular functions. Although conventional cancer treatments significantly contribute to patient recovery, they can also impose many side effects. MiRNAs all significantly regulate angiogenesis, migration, apoptosis, carcinogenesis, and gene expression. Regarding chemotherapy, mounting research indicates that microRNAs may directly influence how responsive leukemia is to chemical treatments. This article reviews current studies on microRNAs, examining their influence on cancer advancement and spread, as well as their possible applications as diagnostic indicators and treatment targets in leukemia. Furthermore, we integrated the functions of microRNAs in cancer formation and progression with leukemia patient care, offering fresh insights into leukemia detection and management strategies.
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Affiliation(s)
- Doha El-Sayed Ellakwa
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy for Girls, Al-Azhar University, Cairo, Egypt.
- Department of Biochemistry, Faculty of Pharmacy, Sinai University, Kantra Branch, Ismailia, Egypt.
| | | | - Mostafa M Mostafa
- Department of Molecular and Cellular Physiology, Stritch School of Medicine, Loyola University Chicago, Chicago, USA
| | - Takwa E Ellakwa
- Physical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
| | - Al-Hassan Soliman Wadan
- Oral Biology Department, Faculty of Dentistry, Galala Plateau, Galala University, 15888), Attaka, Suez Governorate, Egypt
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2
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Nishiwada S, Nakamura K, Ozu N, Terai T, Kohara Y, Nagai M, Sakata T, Doi S, Matsuo Y, Yasuda S, Tanaka T, Sho M. An axon guidance-related microRNA panel identifies perivascular plexus local recurrence following curative surgery in patients with pancreatic cancer. J Gastroenterol 2025:10.1007/s00535-025-02260-w. [PMID: 40347276 DOI: 10.1007/s00535-025-02260-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 04/28/2025] [Indexed: 05/12/2025]
Abstract
BACKGROUND Complete oncological local control is essential for a potential cure in patients with pancreatic ductal adenocarcinoma (PDAC), but predicting local recurrence following curative surgery remains clinically challenging. In this study, we performed comprehensive biomarker discovery to identify an Axon guidance-related miRNA panel (AGMP) for risk-stratification of perivascular plexus recurrence (PPR) following curative surgery in patients with PDAC. METHODS To identify axon guidance-related microRNAs, we performed the pathway-miRNA interaction analysis using the miRPathDB2.0. Subsequently, the predictive performance of the miRNAs was trained and validated in three independent clinical surgically resected sample cohorts and one pretreatment blood sample cohort with different disease statuses [upfront surgery cohort: n = 162 (training: n = 103, internal validation: n = 59), neoadjuvant chemoradiotherapy (NACRT) cohort: n = 217, arterial invasion cohort: n = 62, pretreatment blood sample cohort: n = 53]. RESULTS The pathway-miRNA interaction analysis identified 13 miRNAs related to axon guidance pathway. Subsequently, we trained a 13-miRNA risk-prediction model, AGMP, which robustly distinguished PPR after surgery in the training cohort (AUC = 0.95). The AGMP was successfully validated in three independent cohorts (AUC: validation = 0.94, NACRT = 0.94, Arterial invasion = 0.90). Furthermore, we additionally validated the performance of AGMP in a pretreatment blood cohort, which again confirmed the robustness of risk-stratification for PPR (AUC = 0.86). CONCLUSIONS We developed a novel biomarker, AGMP that demonstrated remarkable predictive performance for PPR following curative surgery in patients with PDAC; highlighting the clinical importance of the nerve-cancer cross-talk and the hopefulness as a guidepost for designing future clinical and basic research to establish individualized treatment strategies.
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Affiliation(s)
- Satoshi Nishiwada
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
- Department of Surgery, Minami-Nara General Medical Center, Nara, Japan
| | - Kota Nakamura
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Naoki Ozu
- Institute for Clinical and Translational Science, Nara Medical University Hospital, Nara, Japan
| | - Taichi Terai
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Yuichiro Kohara
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Minako Nagai
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Takeshi Sakata
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Shunsuke Doi
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Yasuko Matsuo
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Satoshi Yasuda
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Toshihiro Tanaka
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Nara, Japan
| | - Masayuki Sho
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.
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Juthani R, Manne A. Blood-based biomarkers in pancreatic ductal adenocarcinoma: developments over the last decade and what holds for the future- a review. Front Oncol 2025; 15:1555963. [PMID: 40330826 PMCID: PMC12052548 DOI: 10.3389/fonc.2025.1555963] [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: 01/06/2025] [Accepted: 03/24/2025] [Indexed: 05/08/2025] Open
Abstract
Pancreatic Ductal Adenocarcinoma (PDAC) accounts for a significant burden of global cancer deaths worldwide. The dismal outcomes associated with PDAC can be overcome by detecting the disease early and developing tools that predict response to treatment, allowing the selection of the most optimal treatment. Over the last couple of years, significant progress has been made in the development of novel biomarkers that aid in diagnosis, prognosis, treatment selection, and monitoring response. Blood-based biomarkers offer an alternative to tissue-based diagnosis and offer immense potential in managing PDAC. In this review, we have discussed the advances in blood-based biomarkers in PDAC, such as DNA (mutations and methylations), RNA, protein biomarkers and circulating tumor cells (CTC) over the last decade and also elucidated all aspects of practical implementation of these biomarkers in clinical practice. We have also discussed implementing multiomics utilizing more than one biomarker and targeted therapies that have been developed using these biomarkers.
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Affiliation(s)
- Ronit Juthani
- Department of Medicine, Saint Vincent Hospital, Worcester, MA, United States
| | - Ashish Manne
- Department of Internal Medicine, Division of Medical Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States
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Yeat NY, Liu LH, Chang YH, Lai CPK, Chen RH. Bro1 proteins determine tumor immune evasion and metastasis by controlling secretion or degradation of multivesicular bodies. Dev Cell 2025:S1534-5807(25)00155-8. [PMID: 40185104 DOI: 10.1016/j.devcel.2025.03.008] [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: 06/12/2024] [Revised: 11/25/2024] [Accepted: 03/12/2025] [Indexed: 04/07/2025]
Abstract
Exosomes play pleiotropic tumor-promoting functions and are secreted by fusion of multivesicular bodies (MVBs) with the plasma membrane. However, MVBs are also directed to lysosomes for degradation, and the mechanism controlling different fates of MVBs remains elusive. Here, we show that the pro-tumor protein WDR4 enhances exosome secretion from mouse and human cancer cells through degrading the endosomal sorting complex required for transport (ESCRT)-associated Bro1-family protein PTPN23. Mechanistically, PTPN23 and ALIX compete for binding to syntenin, thereby directing MVBs toward degradation and secretion, respectively. ALIX, but not PTPN23, recruits actin-capping proteins CAPZA1/CAPZB to prevent branched filamentous actin (F-actin) accumulation around MVBs, thus enabling MVBs trafficking to the cell periphery for secretion. Functionally, WDR4/ALIX-dependent exosomes load a set of pro-tumor proteins through LAMP2A, thereby potentiating metastasis and immune evasion in mice. Our study highlights a previously unappreciated coupling between the biogenesis mechanism and the fate decision of MVBs and its importance in determining exosomal cargos, which have a profound impact on tumor progression.
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Affiliation(s)
- Nai Yang Yeat
- Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan; Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan
| | - Li-Heng Liu
- Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - Yu-Hsuan Chang
- Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 106, Taiwan
| | | | - Ruey-Hwa Chen
- Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan; Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 106, Taiwan.
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Wollborn L, Webber JW, Alimena S, Mishra S, Sussman CB, Comrie CE, Packard DG, Williams M, Russell T, Fendler W, Chowdhury D, Elias KM. Effects of Clinical Covariates on Serum miRNA Expression among Women without Ovarian Cancer. Cancer Epidemiol Biomarkers Prev 2025; 34:385-393. [PMID: 38780899 PMCID: PMC11873719 DOI: 10.1158/1055-9965.epi-23-1355] [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: 11/02/2023] [Revised: 02/26/2024] [Accepted: 05/20/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND Serum miRNAs are potential biomarkers for ovarian cancer; however, many factors may influence miRNA expression. To understand potential confounders in miRNA analysis, we examined how sociodemographic factors and comorbidities, including known ovarian cancer risk factors, influence serum miRNA levels in women without ovarian cancer. METHODS Data from 1,576 women from the Mass General Brigham Biobank collected between 2012 and 2019, excluding subjects previously or subsequently diagnosed with ovarian cancer, were examined. Using a focused panel of 179 miRNA probes optimized for serum profiling, miRNA expression was measured by flow cytometry using the Abcam FirePlex assay and correlated with subjects' electronic medical records. RESULTS The study population broadly reflected the New England population. The median age of subjects was 49 years, 34% were current or prior smokers, 33% were obese (body mass index > 30 kg/m2), 49% were postmenopausal, and 11% had undergone prior bilateral oophorectomy. Significant differences in miRNA expression were observed among ovarian risk factors such as age, obesity, menopause, BRCA1 or BRCA2 germline mutations, or existence of breast cancer in family history. Additionally, miRNA expression was significantly altered by prior bilateral oophorectomy, hypertension, and hypercholesterolemia. Other variables, such as smoking; parity; age at menarche; hormonal replacement therapy; oral contraception; breast, endometrial, or colon cancer; and diabetes, were not associated with significant changes in the panel when corrected for multiple testing. CONCLUSIONS Serum miRNA expression patterns are significantly affected by patient demographics, exposure history, and medical comorbidities. IMPACT Understanding confounders in serum miRNA expression is important for refining clinical assays for cancer screening.
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Affiliation(s)
- Laura Wollborn
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, Massachusetts
| | - James W. Webber
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, Massachusetts
| | - Stephanie Alimena
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, Massachusetts
| | - Sudhanshu Mishra
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, Massachusetts
| | | | | | | | | | | | - Wojciech Fendler
- Dana-Farber Cancer Institute, Boston, Massachusetts
- Department of Biostatistics and Translational Medicine, Medical University of Łódź, Łódź, Poland
| | - Dipanjan Chowdhury
- Harvard Medical School, Boston, Massachusetts
- Dana-Farber Cancer Institute, Boston, Massachusetts
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Kevin M. Elias
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
- Dana-Farber Cancer Institute, Boston, Massachusetts
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Rouhi S, Ghasemi H, Alizadeh M, Movahedpour A, Vahedi F, Fattahi M, Aiiashi S, Khatami SH. miRNA-based electrochemical biosensors for ovarian cancer. Clin Chim Acta 2025; 564:119946. [PMID: 39214394 DOI: 10.1016/j.cca.2024.119946] [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: 03/01/2024] [Revised: 08/22/2024] [Accepted: 08/25/2024] [Indexed: 09/04/2024]
Abstract
Ovarian cancer, a prevalent and deadly cancer among women, presents a significant challenge for early detection due to its heterogeneous nature. MicroRNAs, short non-coding regulatory RNA fragments, play a role in various cellular processes. Aberrant expression of these microRNAs has been observed in the carcinogenesis-related processes of many cancer types. Numerous studies highlight the critical role of microRNAs in the initiation and progression of ovarian cancer. Given their clinical importance and predictive value, there has been considerable interest in developing simple, prompt, and sensitive miRNA biosensor strategies. Among these, electrochemical sensors have demonstrated advantageous characteristics such as simplicity, sensitivity, low cost, and scalability. These microRNA-based electrochemical biosensors are valuable tools for early detection and point-of-care applications. This article discusses the potential role of microRNAs in ovarian cancer and recent advances in the development of electrochemical biosensors for miRNA detection in ovarian cancer samples.
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Affiliation(s)
- Saber Rouhi
- Resident of Large Animal Internal Medicine, Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Iran
| | | | - Mehdi Alizadeh
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmad Movahedpour
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Farzaneh Vahedi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Mehdi Fattahi
- Institute of Research and Development, Duy Tan University, Da Nang, Viet Nam; School of Engineering & Technology, Duy Tan University, Da Nang, Viet Nam
| | - Saleh Aiiashi
- Abadan University of Medical Sciences, Abadan, Iran.
| | - Seyyed Hossein Khatami
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Tripathi S, Sharma Y, Kumar D. Biological Cargo: Exosomes and their Role in Cancer Progression and Metastasis. Curr Top Med Chem 2025; 25:263-285. [PMID: 38984577 DOI: 10.2174/0115680266304636240626055711] [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: 01/16/2024] [Revised: 05/23/2024] [Accepted: 05/23/2024] [Indexed: 07/11/2024]
Abstract
Cancer cells are among the many types of cells that release exosomes, which are nanovesicles. Because of their many potential applications, exosomes have recently garnered much attention from cancer researchers. The bioactive substances that exosomes release as cargo have been the subject of several investigations. The substances in question may operate as biomarkers for diagnosis or affect apoptosis, the immune system, the development and spread of cancer, and other processes. Others have begun to look at exosomes in experimental therapeutic trials because they believe they may be useful in the treatment of cancer. This review started with a short description of exosome biogenesis and key features. Next, the potential of tumor-derived exosomes and oncosomes to influence the immune system throughout the development of cancer, as well as alter tumor microenvironments (TMEs) and pre-metastatic niche creation, was investigated. Finally, there was talk of exosomes' possible use in cancer treatment. Furthermore, there is emerging consensus about the potential application of exosomes to be biological reprogrammers of cancer cells, either as carriers of naturally occurring chemicals, including anticancer medications, or as carriers of anticancer vaccines for immunotherapy as well as boron neutron capture therapy (BNCT). We briefly review the key ideas and logic behind this intriguing therapy recommendation.
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Affiliation(s)
- Siddhant Tripathi
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, 411038, India
| | - Yashika Sharma
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, 411038, India
| | - Dileep Kumar
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, 411038, India
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Zaib S, Javed H, Rana N, Zaib Z, Iqbal S, Khan I. Therapeutic Chemoresistance in Ovarian Cancer: Emerging Hallmarks, Signaling Mechanisms and Alternative Pathways. Curr Med Chem 2025; 32:923-938. [PMID: 38275065 DOI: 10.2174/0109298673276871231205043417] [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: 08/11/2023] [Revised: 10/28/2023] [Accepted: 10/31/2023] [Indexed: 01/27/2024]
Abstract
Ovarian cancer is the fifth leading cause of mortality and the most lethal gynecologic malignancy among females. It may arise from atypical borderline tumors (Type I) or serous tubal intraepithelial carcinoma (Type II). The diagnosis of cancer at its early stages is difficult because of non-specific symptoms, most patients are diagnosed at the advanced stage. Several drugs and therapeutic strategies are available to treat ovarian cancer such as surgery, chemotherapy, neoadjuvant therapy, and maintenance therapy. However, the cancer cells have developed resistance to a number of available therapies causing treatment failure. This emerging chemoresistance in ovarian cancer cells is becoming an obstacle due to alterations in multiple cellular processes. These processes involve altered drug target response, drug pumps, detoxification systems, lower sensitivity to apoptosis, and altered proliferation, and are responsible for developing resistance to anticancer medicines. Various research reports have evidenced that these altered processes might play a role in the emergence of resistance. This review addresses the recent advances in understanding the underlying mechanisms of ovarian cancer resistance and covers sophisticated alternative pathways to overcome these resistance mechanisms in patients.
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Affiliation(s)
- Sumera Zaib
- Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore, 54590, Pakistan
| | - Hira Javed
- Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore, 54590, Pakistan
| | - Nehal Rana
- Department of Basic and Applied Chemistry, Faculty of Science and Technology, University of Central Punjab, Lahore, 54590, Pakistan
| | - Zainab Zaib
- Combined Military Hospital Abbottabad, Abbottabad, 22010, Pakistan
| | - Shahid Iqbal
- Department of Chemistry, School of Natural Sciences (SNS), National University of Science and Technology (NUST), H-12, Islamabad, 46000, Pakistan
| | - Imtiaz Khan
- Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, United Kingdom
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Oliveira FD, Cavaco M, Figueira TN, Napoleão P, Valle J, Neves V, Andreu D, Castanho MA. vCPP2319 interacts with metastatic breast cancer extracellular vesicles (EVs) and transposes a human blood-brain barrier model. Heliyon 2024; 10:e40907. [PMID: 39717586 PMCID: PMC11664409 DOI: 10.1016/j.heliyon.2024.e40907] [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: 04/06/2024] [Revised: 12/02/2024] [Accepted: 12/03/2024] [Indexed: 12/25/2024] Open
Abstract
Brain metastases (BM) are frequently found in cancer patients and, though their precise incidence is difficult to estimate, there is evidence for a correlation between BM and specific primary cancers, such as lung, breast, and skin (melanoma). Among all these, breast cancer is the most frequently diagnosed among women and, in this case, BM cause a critical reduction of the overall survival (OS), especially in triple negative breast cancer (TNBC) patients. The main challenge of BM treatment is the impermeable nature of the blood-brain barrier (BBB), which shields the central nervous systems (CNS) from chemotherapeutic drugs. Extracellular vesicles (EVs) have been proposed as ideal natural drug carriers and these may exhibit some advantages over synthetic nanoparticles (NPs). In this work, we isolate breast cancer-derived EVs and study their ability to carry vCPP2319, a peptide with dual cell-penetration and anticancer activities. The selective cytotoxicity of anticancer peptide-loaded EVs towards breast cancer cells and their ability to translocate an in vitro BBB model are also addressed. Overall, it was possible to conclude that vCPP2319 naturally interacts with breast cancer-derived EVs, being retained at the surface of these vesicles. Moreover, the results revealed a cytotoxic activity for peptide-loaded EVs similar to that obtained with the peptide alone and the ability of peptide-loaded EVs to translocate an in vitro BBB model, which contrasts with the results obtained with the peptide alone. In conclusion, this work supports the use of EVs in the development of biological drug-delivery systems (DDS) capable of translocating the BBB.
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Affiliation(s)
- Filipa D. Oliveira
- Gulbenkian Institute for Molecular Medicine, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon, 1649-028, Portugal
| | - Marco Cavaco
- Gulbenkian Institute for Molecular Medicine, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon, 1649-028, Portugal
| | - Tiago N. Figueira
- Gulbenkian Institute for Molecular Medicine, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon, 1649-028, Portugal
| | - Patrícia Napoleão
- Gulbenkian Institute for Molecular Medicine, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon, 1649-028, Portugal
| | - Javier Valle
- Department of Medicine and Life Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park, 08003, Barcelona, Spain
| | - Vera Neves
- Gulbenkian Institute for Molecular Medicine, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon, 1649-028, Portugal
| | - David Andreu
- Department of Medicine and Life Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park, 08003, Barcelona, Spain
| | - Miguel A.R.B. Castanho
- Gulbenkian Institute for Molecular Medicine, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, Lisbon, 1649-028, Portugal
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Soni N, Bissa B. Exosomes, circadian rhythms, and cancer precision medicine: New frontiers. Biochimie 2024; 227:172-181. [PMID: 39032591 DOI: 10.1016/j.biochi.2024.07.010] [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: 12/12/2023] [Revised: 07/01/2024] [Accepted: 07/10/2024] [Indexed: 07/23/2024]
Abstract
"The environment shapes people's actions," a well-known proverb, strongly dictates that a change in our way of life changes our behavior. Circadian rhythms have been identified as a mechanism for maintaining homeostasis in the body, which, if disrupted by sleeping patterns, could result in significant metabolic alterations that adversely affect our health. The changes induced by circadian rhythm alter the secretion and cargo selection in exosomes which are nanovesicles important for intercellular communication. Exosomes were formerly known as "junk particles" but are now recognized as miniature copies of a cell's genetic material. Dysregulation of circadian rhythm has shown that it changes the gene expression of a cell to some extent and significantly alters the exosomal release. Meanwhile, cells secrete exosomes continuously to align the rhythmicity of the biological clock. In this study, we integrate circadian rhythms and exosomes with precision medicines to find better approaches to early diagnosis and treatment of disease.
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Affiliation(s)
- Naveen Soni
- Dept. of Biochemistry, Central University of Rajasthan, Ajmer, Rajasthan, India
| | - Bhawana Bissa
- Dept. of Biochemistry, Central University of Rajasthan, Ajmer, Rajasthan, India.
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11
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Aslan C, Zolbanin NM, Faraji F, Jafari R. Exosomes for CRISPR-Cas9 Delivery: The Cutting Edge in Genome Editing. Mol Biotechnol 2024; 66:3092-3116. [PMID: 38012525 DOI: 10.1007/s12033-023-00932-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 10/02/2023] [Indexed: 11/29/2023]
Abstract
Gene mutation correction was challenging until the discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas). CRISPR is a new era for genome modification, and this technology has bypassed the limitations of previous methods such as zinc-finger nuclease and transcription activator-like effector nuclease. Currently, this method is becoming the method of choice for gene-editing purposes, especially therapeutic gene editing in diseases such as cardiovascular, neurological, renal, genetic, optical, and stem cell, as well as blood disorders and muscular degeneration. However, finding the optimum delivery system capable of carrying this large complex persists as the main challenge of this technology. Therefore, it would be ideal if the delivery vehicle could direct the introduction of editing functions to specific cells in a multicellular organism. Exosomes are membrane-bound vesicles with high biocompatibility and low immunogenicity; they offer the best and most reliable way to fill the CRISPR/Cas9 system delivery gap. This review presents the current evidence on the molecular mechanisms and challenges of CRISPR/Cas9-mediated genome modification. Also, the role of CRISPR/Cas9 in the development of treatment and diagnosis of numerous disorders, from malignancies to viral infections, has been discussed. Lastly, the focus is on new advances in exosome-delivery technologies that may play a role in CRISPR/Cas9 delivery for future clinical settings.
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Affiliation(s)
- Cynthia Aslan
- Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Naime Majidi Zolbanin
- Experimental and Applied Pharmaceutical Sciences Research Center, Urmia University of Medical Sciences, Urmia, Iran
- Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
| | - Fatemeh Faraji
- Hazrat-e Rasool General Hospital, Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Floor 3, Building No. 3, Niyayesh St, Sattar Khan St, Tehran, 1445613131, Iran.
| | - Reza Jafari
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Clinical Research Institute, Urmia University of Medical Sciences, Shafa St., Ershad Blvd., P.O. Box: 1138, Urmia, 57147, Iran.
- Department of Immunology and Genetics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
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Bates M, Mohamed BM, Lewis F, O'Toole S, O'Leary JJ. Biomarkers in high grade serous ovarian cancer. Biochim Biophys Acta Rev Cancer 2024; 1879:189224. [PMID: 39581234 DOI: 10.1016/j.bbcan.2024.189224] [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: 01/28/2024] [Revised: 11/15/2024] [Accepted: 11/15/2024] [Indexed: 11/26/2024]
Abstract
High-grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. HGSC patients typically present with advanced disease, which is often resistant to chemotherapy and recurs despite initial responses to therapy, resulting in the poor prognosis associated with this disease. There is a need to utilise biomarkers to manage the various aspects of HGSC patient care. In this review we discuss the current state of biomarkers in HGSC, focusing on the various available immunohistochemical (IHC) and blood-based biomarkers, which have been examined for their diagnostic, prognostic and theranostic potential in HGSC. These include various routine clinical IHC biomarkers such as p53, WT1, keratins, PAX8, Ki67 and p16 and clinical blood-borne markers and algorithms such as CA125, HE4, ROMA, RMI, ROCA, and others. We also discuss various components of the liquid biopsy as well as a number of novel IHC biomarkers and non-routine blood-borne biomarkers, which have been examined in various ovarian cancer studies. We also discuss the future of ovarian cancer biomarker research and highlight some of the challenges currently facing the field.
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Affiliation(s)
- Mark Bates
- Department of Histopathology, Trinity College Dublin, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin, Ireland; Trinity St James's Cancer Institute, Dublin, Ireland.
| | - Bashir M Mohamed
- Department of Histopathology, Trinity College Dublin, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin, Ireland; Trinity St James's Cancer Institute, Dublin, Ireland
| | - Faye Lewis
- Department of Histopathology, Trinity College Dublin, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin, Ireland; Trinity St James's Cancer Institute, Dublin, Ireland
| | - Sharon O'Toole
- Department of Histopathology, Trinity College Dublin, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin, Ireland; Trinity St James's Cancer Institute, Dublin, Ireland; Department of Obstetrics and Gynaecology, Trinity College Dublin, Dublin, Ireland
| | - John J O'Leary
- Department of Histopathology, Trinity College Dublin, Dublin, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin, Ireland; Trinity St James's Cancer Institute, Dublin, Ireland; Department of Pathology, Coombe Women & Infants University Hospital, Dublin, Ireland
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13
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Tripathi AD, Labh Y, Katiyar S, Chaturvedi VK, Sharma P, Mishra A. Advancements in Nano-Mediated Biosensors: Targeting Cancer Exosome Detection. J CLUST SCI 2024; 35:2195-2212. [DOI: 10.1007/s10876-024-02676-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 07/24/2024] [Indexed: 01/05/2025]
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14
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Sazaklioglu SA, Torul H, Tamer U, Ensarioglu HK, Vatansever HS, Gumus BH, Çelikkan H. Sensitive and reliable lab-on-paper biosensor for label-free detection of exosomes by electrochemical impedance spectroscopy. Mikrochim Acta 2024; 191:617. [PMID: 39316098 DOI: 10.1007/s00604-024-06644-2] [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: 07/10/2024] [Accepted: 08/19/2024] [Indexed: 09/25/2024]
Abstract
A new, sensitive, and cost-effective lab-on-paper-based immunosensor was designed based on electrochemical impedance spectroscopy (EIS) for the detection of exosomes. EIS was selected as the determination method since there was a surface blockage in electron transfer by binding the exosomes to the transducer. Briefly, the carbon working electrode (WE) on the paper electrode (PE) was modified with gold particles (AuPs@PE) and then conjugated with anti-CD9 (Anti-CD9/AuPs@PE) for the detection of exosomes. Variables involved in the biosensor design were optimized with the univariate mode. The developed method presents the limit of detection of 8.7 × 102 exosomes mL-1, which is lower than that of many other available methods under the best conditions. The biosensor was also tested with urine samples from cancer patients with high recoveries. Due to this a unique, low-cost, biodegradable technology is presented that can directly measure exosomes without labeling them for early cancer or metastasis detection.
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Affiliation(s)
- Sevda Akay Sazaklioglu
- Faculty of Pharmacy, Department of Analytical Chemistry, Ankara Medipol University, 06050, Ankara, Turkey
- Graduate School of Natural and Applied Science, Gazi University, 06560, Ankara, Turkey
| | - Hilal Torul
- Faculty of Pharmacy, Department of Analytical Chemistry, Gazi University, 06330, Ankara, Turkey
| | - Uğur Tamer
- Faculty of Pharmacy, Department of Analytical Chemistry, Gazi University, 06330, Ankara, Turkey
- METU MEMS Center, Ankara, Turkey
| | - Hilal Kabadayi Ensarioglu
- Faculty of Medicine, Department of Histology and Embryology, Manisa Celal Bayar University, 45200, Manisa, Turkey
| | - Hafize Seda Vatansever
- Faculty of Medicine, Department of Histology and Embryology, Manisa Celal Bayar University, 45200, Manisa, Turkey
- DESAM Institute, Near East University, Mersin 10, Turkey
| | - Bilal H Gumus
- Faculty of Medicine, Department of Urology, Manisa Celal Bayar University, 45200, Manisa, Turkey
| | - Hüseyin Çelikkan
- Faculty of Science, Department of Chemistry, Gazi University, 06560, Ankara, Turkey.
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Luan W, Lu X, Peng H, Shen X, Rao M, Ruan H. Exosomal miR-19a derived from melanoma cell promotes the vemurafenib resistance of malignant melanoma through directly targeting LRIG1 to reactivate AKT and MAPK pathway. Pathol Res Pract 2024; 260:155410. [PMID: 38955119 DOI: 10.1016/j.prp.2024.155410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 04/04/2024] [Accepted: 06/13/2024] [Indexed: 07/04/2024]
Abstract
Exosomes derived from neighboring v-raf murine sarcoma viral oncogene homolog B1 inhibitor (BRAFi)-resistant melanoma cells mediate the formation of resistance in melanoma cells sensitive to BRAFi. The function and molecular mechanisms of exosomal miRNA in BRAFi resistance of melanoma have not been studied. We found that the expression of miR-19a in BRAFi resistant melanoma cells was significantly higher than that in sensitive cells, and miR-19a contributes to the resistance of melanoma cells to BRAFi by targeting immunoglobulin-like domains protein 1 (LRIG1). miR-19a was highly enriched in exosomes secreted from BRAFi resistant melanoma cells, and these exosomal miR-19a promote the spread of BRAFi resistant. The reactivation of Protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) pathways is the main reason for the BRAFi resistant of melanoma cells. We demonstrated that exosomal miR-19a derived from melanoma cell promotes the formation and spread of BRAFi resistant in melanoma through targeting LRIG1 to reactivate AKT and MAPK pathway. Therefore, miR-19a may serve as a potential therapeutic target in melanoma patients with acquired drug resistance.
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Affiliation(s)
- Wenkang Luan
- Department of Plastic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xu Lu
- Department of Plastic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Huiyong Peng
- Department of Laboratory Medicine, The Affiliated People's Hospital of Jiangsu University, Zhenjiang Medical School of Nanjing Medical University, Zhenjiang, Jiangsu, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xuanlin Shen
- Department of Rehabilitation, Changshu No. 2 People's Hospital (Changshu Hospital affiliated the NanTong University), Changshu, Jiangsu 215500, China
| | - Min Rao
- Hepatobiliary surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Hongru Ruan
- Department of Plastic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
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16
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Lu T, Zheng Y, Chen X, Lin Z, Liu C, Yuan C. The role of exosome derived miRNAs in inter-cell crosstalk among insulin-related organs in type 2 diabetes mellitus. J Physiol Biochem 2024; 80:501-510. [PMID: 38698251 DOI: 10.1007/s13105-024-01026-x] [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: 09/07/2023] [Accepted: 04/23/2024] [Indexed: 05/05/2024]
Abstract
Exosomes are small extracellular vesicles secreted by almost all cell types, and carry diverse cargo including RNA, and other substances. Recent studies have focused exosomal microRNAs (miRNAs) on various human diseases, including type 2 diabetes mellitus (T2DM) and metabolic syndrome (METS) which accompany the occurrence of insulin resistance. The regulation of insulin signaling has connected with some miRNA expression which play a significant regulatory character in insulin targeted cells or organs, such as fat, muscle, and liver. The miRNAs carried by exosomes, through the circulation in the body fluids, mediate all kinds of physiological and pathological process involved in the human body. Studies have found that exosome derived miRNAs are abnormally expressed and cross-talked with insulin targeted cells or organs to affect insulin pathways. Further investigations of the mechanisms of exosomal miRNAs in T2DM will be valuable for the diagnostic biomarkers and therapeutic targets of T2DM. This review will summarize the molecular mechanism of action of the miRNAs carried by exosomes which are secreted from insulin signaling related cells, and elucidate the pathogenesis of insulin resistance to provide a new strategy for the potential diagnostic biomarkers and therapeutic targets for the type 2 diabetes.
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Affiliation(s)
- Ting Lu
- Tumor Microenvironment and Immunotherapy Key Laboratory of Hubei province in China, China Three Gorges University, School of Medicine, Yichang, 443002, China
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China
| | - Ying Zheng
- Tumor Microenvironment and Immunotherapy Key Laboratory of Hubei province in China, China Three Gorges University, School of Medicine, Yichang, 443002, China
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China
| | - Xiaoling Chen
- Tumor Microenvironment and Immunotherapy Key Laboratory of Hubei province in China, China Three Gorges University, School of Medicine, Yichang, 443002, China
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China
| | - Zhiyong Lin
- Tumor Microenvironment and Immunotherapy Key Laboratory of Hubei province in China, China Three Gorges University, School of Medicine, Yichang, 443002, China
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China
| | - Chaoqi Liu
- Tumor Microenvironment and Immunotherapy Key Laboratory of Hubei province in China, China Three Gorges University, School of Medicine, Yichang, 443002, China.
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China.
| | - Chengfu Yuan
- Tumor Microenvironment and Immunotherapy Key Laboratory of Hubei province in China, China Three Gorges University, School of Medicine, Yichang, 443002, China.
- College of Basic Medical Science, China Three Gorges University, Yichang, 443002, China.
- Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, China Three Gorges University, School of Medicine, Yichang, 443002, China.
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17
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Tamimi A, Javid M, Sedighi-Pirsaraei N, Mirdamadi A. Exosome prospects in the diagnosis and treatment of non-alcoholic fatty liver disease. Front Med (Lausanne) 2024; 11:1420281. [PMID: 39144666 PMCID: PMC11322140 DOI: 10.3389/fmed.2024.1420281] [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: 04/19/2024] [Accepted: 07/16/2024] [Indexed: 08/16/2024] Open
Abstract
The growing prevalence of NAFLD and its global health burden have provoked considerable research on possible diagnostic and therapeutic options for NAFLD. Although various pathophysiological mechanisms and genetic factors have been identified to be associated with NAFLD, its treatment remains challenging. In recent years, exosomes have attracted widespread attention for their role in metabolic dysfunctions and their efficacy as pathological biomarkers. Exosomes have also shown tremendous potential in treating a variety of disorders. With increasing evidence supporting the significant role of exosomes in NAFLD pathogenesis, their theragnostic potential has become a point of interest in NAFLD. Expectedly, exosome-based treatment strategies have shown promise in the prevention and amelioration of NAFLD in preclinical studies. However, there are still serious challenges in preparing, standardizing, and applying exosome-based therapies as a routine clinical option that should be overcome. Due to the great potential of this novel theragnostic agent in NAFLD, further investigations on their safety, clinical efficacy, and application standardization are highly recommended.
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Pal R, Choudhury T, Ghosh M, Vernakar M, Nath P, Nasare VD. A signature of circulating miRNAs predicts the prognosis and therapeutic outcome of taxane/platinum regimen in advanced ovarian carcinoma patients. Clin Transl Oncol 2024; 26:1716-1724. [PMID: 38472557 DOI: 10.1007/s12094-024-03394-8] [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: 12/13/2023] [Accepted: 01/19/2024] [Indexed: 03/14/2024]
Abstract
PURPOSE Ovarian carcinoma (OC) is ranked as the eighth most lethal gynecological cancer due to late diagnosis and high recurrence. Existing biomarkers are lacking to predict the recurrence and stratify patients who are likely to benefit from chemotherapy. MicroRNAs (miRNAs/miRs) are persistently present in humans and are capable of predicting treatment outcomes. Thus, the purpose of the study was to assess the potential of circulatory miRNAs to predict the efficacy of OC. METHODS Newly diagnosed n = 208 OC patients were administrated neoadjuvant/adjuvant chemotherapy (taxane + platinum) after surgery. Their demographic, gynecologic, clinical parameters, response, and survival were recorded. MiR-27a, miR-182, miR-199a, miR-214, and miR-591 were taken and the expression were analyzed using real-time PCR at different treatment intervals. Further, its prognostic value (Kaplan-Meier, and Cox regression analysis) and diagnostic importance (receiver operating characteristic curve) were validated. RESULT The mean age of patients with poorly differentiated (45.2%) serous OC was 48.69 ± 10.38. The majority experienced menarche at ≥ 12 (62.2%) with poor menstrual hygiene (81.8%) and were post-menopausal (69.4%), some were associated with high risk of survival (HR = > 1). MiRNA signature showed three over-expression and two under-expression (miR-27a, miR-182, and miR-214; miR-199a and miR-591) in advanced OC compared to the control (P= < 0.05). Also, a significant difference was detected at each time interval of treatment with the response (P = ≤ 0.001) associated with resistance and overall survival (P = ≤ 0.001) with risk (HR = > 1). ROC analysis showed enhanced the diagnostics accuracy (< 0.001). CONCLUSION Our findings indicate that circulating miRNAs might be a potential minimally invasive diagnostic marker for treatment outcome and recurrence in ovarian carcinoma.
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Affiliation(s)
- Ranita Pal
- Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India
- Department of Zoology, University of Calcutta, 35, Ballygunge Circular Rd, Kolkata, 700019, India
| | - Trisha Choudhury
- Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India
| | - Madhurima Ghosh
- Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India
| | - Manisha Vernakar
- Department of Gynaecological Oncology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India
| | - Partha Nath
- Department of Medical Oncology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India
| | - Vilas Deorao Nasare
- Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India.
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19
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Wang F, Zhou C, Zhu Y, Keshavarzi M. The microRNA Let-7 and its exosomal form: Epigenetic regulators of gynecological cancers. Cell Biol Toxicol 2024; 40:42. [PMID: 38836981 PMCID: PMC11153289 DOI: 10.1007/s10565-024-09884-3] [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: 01/31/2024] [Accepted: 05/15/2024] [Indexed: 06/06/2024]
Abstract
Many types of gynecological cancer (GC) are often silent until they reach an advanced stage, and are therefore often diagnosed too late for effective treatment. Hence, there is a real need for more efficient diagnosis and treatment for patients with GC. During recent years, researchers have increasingly studied the impact of microRNAs cancer development, leading to a number of applications in detection and treatment. MicroRNAs are a particular group of tiny RNA molecules that regulate regular gene expression by affecting the translation process. The downregulation of numerous miRNAs has been observed in human malignancies. Let-7 is an example of a miRNA that controls cellular processes as well as signaling cascades to affect post-transcriptional gene expression. Recent research supports the hypothesis that enhancing let-7 expression in those cancers where it is downregulated may be a potential treatment option. Exosomes are tiny vesicles that move through body fluids and can include components like miRNAs (including let-7) that are important for communication between cells. Studies proved that exosomes are able to enhance tumor growth, angiogenesis, chemoresistance, metastasis, and immune evasion, thus suggesting their importance in GC management.
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Affiliation(s)
- Fei Wang
- Haiyan People's Hospital, Zhejiang Province, Jiaxing, 314300, Zhejiang, China
| | - Chundi Zhou
- Haiyan People's Hospital, Zhejiang Province, Jiaxing, 314300, Zhejiang, China
| | - Yanping Zhu
- Haiyan People's Hospital, Zhejiang Province, Jiaxing, 314300, Zhejiang, China.
| | - Maryam Keshavarzi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Tehran, Iran.
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20
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Ahmadpour S, Habibi MA, Ghazi FS, Molazadeh M, Pashaie MR, Mohammadpour Y. The effects of tumor-derived supernatants (TDS) on cancer cell progression: A review and update on carcinogenesis and immunotherapy. Cancer Treat Res Commun 2024; 40:100823. [PMID: 38875884 DOI: 10.1016/j.ctarc.2024.100823] [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: 04/25/2024] [Revised: 05/26/2024] [Accepted: 05/27/2024] [Indexed: 06/16/2024]
Abstract
Tumors can produce bioactive substances called tumor-derived supernatants (TDS) that modify the immune response in the host body. This can result in immunosuppressive effects that promote the growth and spread of cancer. During tumorigenesis, the exudation of these substances can disrupt the function of immune sentinels in the host and reinforce the support for cancer cell growth. Tumor cells produce cytokines, growth factors, and proteins, which contribute to the progression of the tumor and the formation of premetastatic niches. By understanding how cancer cells influence the host immune system through the secretion of these factors, we can gain new insights into cancer diagnosis and therapy.
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Affiliation(s)
- Sajjad Ahmadpour
- Patient Safety Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohammad Amin Habibi
- Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mikaeil Molazadeh
- Department of Medical Physics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Reza Pashaie
- Patient Safety Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran; Department of Internal Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Yousef Mohammadpour
- Department of Medical Education, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
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21
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Suartz CV, Martinez LM, Cordeiro MD, Botelho LAA, Gallutti FP, Mota JM, Leite KRM, Toren P, Nahas WC, Ribeiro-Filho LA. Honing the Hunt: A Comprehensive Review of Cell-free Tumor DNA to Predict Neoadjuvant Therapy Efficacy in Bladder Cancer. Clin Genitourin Cancer 2024; 22:102087. [PMID: 38688207 DOI: 10.1016/j.clgc.2024.102087] [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: 12/16/2023] [Accepted: 03/29/2024] [Indexed: 05/02/2024]
Abstract
OBJECTIVE To provide an updated view on the role of cell-free DNA as a predictor of pathological response to neoadjuvant therapy in patients with muscle-invasive bladder cancer. METHODS A systematic review was conducted from September 2023 to October 2023. Selected studies from the MEDLINE and clinical trial databases were critically analyzed regarding the clinical efficacy of cell-free DNA as a predictive instrument after neoadjuvant therapy in bladder cancer. The methodological quality assessment was based on the QUADAS-2 tool. RESULTS In this systematic review, we analyzed 5 studies encompassing a cumulative patient cohort of 780 individuals diagnosed with muscle-invasive bladder cancer, with a median follow-up ranging from 6 to 23 months. Among these studies, 4 primarily focused on detecting and analyzing circulating tumor DNA in plasma, while 1 study uniquely utilized cell-free tumor DNA in urine samples. The diagnostic accuracy of cell-free DNA in plasma ranges from 79% to 100%, indicating a variable yet significant predictive capability. In contrast, the study utilizing urinary cell-free DNA demonstrated an accuracy of 81% in predicting treatment response post-neoadjuvant chemotherapy. CONCLUSION Cell-free DNA is emerging as a valuable biomarker for predicting response to neoadjuvant chemotherapy in patients with muscle-invasive bladder tumors.
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Affiliation(s)
- Caio V Suartz
- Division of Urology, Institute of Cancer of São Paulo, University of São Paulo, Brazil; Division of Urology, Department of Surgery, CHU de Québec - Université Laval, Quebec City, QC, Canada.
| | - Lucas Motta Martinez
- Division of Urology, Institute of Cancer of São Paulo, University of São Paulo, Brazil
| | - Maurício D Cordeiro
- Division of Urology, Institute of Cancer of São Paulo, University of São Paulo, Brazil
| | - Luiz A A Botelho
- Division of Urology, Institute of Cancer of São Paulo, University of São Paulo, Brazil
| | - Fábio P Gallutti
- Division of Urology, Institute of Cancer of São Paulo, University of São Paulo, Brazil
| | - José M Mota
- Genitourinary Medical Oncology Service, Institute of Cancer of São Paulo, University of São Paulo, Brazil
| | - Katia R M Leite
- Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil
| | - Paul Toren
- Division of Urology, Department of Surgery, CHU de Québec - Université Laval, Quebec City, QC, Canada
| | - William C Nahas
- Division of Urology, Institute of Cancer of São Paulo, University of São Paulo, Brazil
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Tiwari P, Yadav K, Shukla RP, Bakshi AK, Panwar D, Das S, Mishra PR. Extracellular vesicles-powered immunotherapy: Unleashing the potential for safer and more effective cancer treatment. Arch Biochem Biophys 2024; 756:110022. [PMID: 38697343 DOI: 10.1016/j.abb.2024.110022] [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: 03/20/2024] [Revised: 04/29/2024] [Accepted: 04/29/2024] [Indexed: 05/04/2024]
Abstract
Cancer treatment has seen significant advancements with the introduction of Onco-immunotherapies (OIMTs). Although some of these therapies have received approval for use, others are either undergoing testing or are still in the early stages of development. Challenges persist in making immunotherapy widely applicable to cancer treatment. To maximize the benefits of immunotherapy and minimize potential side effects, it's essential to improve response rates across different immunotherapy methods. A promising development in this area is the use of extracellular vesicles (EVs) as novel delivery systems. These small vesicles can effectively deliver immunotherapies, enhancing their effectiveness and reducing harmful side effects. This article discusses the importance of integrating nanomedicines into OIMTs, highlighting the challenges with current anti-OIMT methods. It also explores key considerations for designing nanomedicines tailored for OIMTs, aiming to improve upon existing immunotherapy techniques. Additionally, the article looks into innovative approaches like biomimicry and the use of natural biomaterial-based nanocarriers (NCs). These advancements have the potential to transform the delivery of immunotherapy. Lastly, the article addresses the challenges of moving OIMTs from theory to clinical practice, providing insights into the future of using advanced nanotechnology in cancer treatment.
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Affiliation(s)
- Pratiksha Tiwari
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India; Jawaharlal Nehru University, New Delhi, India
| | - Krishna Yadav
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India
| | - Ravi Prakash Shukla
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India
| | - Avijit Kumar Bakshi
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India
| | - Dilip Panwar
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India
| | - Sweety Das
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India
| | - Prabhat Ranjan Mishra
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute Lucknow, India; Academy of Scientific and Innovation Research (AcSIR), Ghaziabad, 201002, U.P., India.
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23
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Amiri M, Kaviari MA, Rostaminasab G, Barimani A, Rezakhani L. A novel cell-free therapy using exosomes in the inner ear regeneration. Tissue Cell 2024; 88:102373. [PMID: 38640600 DOI: 10.1016/j.tice.2024.102373] [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: 12/22/2023] [Revised: 03/01/2024] [Accepted: 04/03/2024] [Indexed: 04/21/2024]
Abstract
Cellular and molecular alterations associated with hearing loss are now better understood with advances in molecular biology. These changes indicate the participation of distinct damage and stress pathways that are unlikely to be fully addressed by conventional pharmaceutical treatment. Sensorineural hearing loss is a common and debilitating condition for which comprehensive pharmacologic intervention is not available. The complex and diverse molecular pathology that underlies hearing loss currently limits our ability to intervene with small molecules. The present review focuses on the potential for the use of extracellular vesicles in otology. It examines a variety of inner ear diseases and hearing loss that may be treatable using exosomes (EXOs). The role of EXOs as carriers for the treatment of diseases related to the inner ear as well as EXOs as biomarkers for the recognition of diseases related to the ear is discussed.
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Affiliation(s)
- Masoumeh Amiri
- Faculty of Medicine, Kermanshah University of Medical Science, Kermanshah, Iran
| | - Mohammad Amin Kaviari
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran; Universal Scientific Education and Research Network (USERN) Office, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Gelavizh Rostaminasab
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amir Barimani
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Leila Rezakhani
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Bhavsar D, Raguraman R, Kim D, Ren X, Munshi A, Moore K, Sikavitsas V, Ramesh R. Exosomes in diagnostic and therapeutic applications of ovarian cancer. J Ovarian Res 2024; 17:113. [PMID: 38796525 PMCID: PMC11127348 DOI: 10.1186/s13048-024-01417-0] [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: 08/21/2023] [Accepted: 04/16/2024] [Indexed: 05/28/2024] Open
Abstract
Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons for the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic and therapeutic options for ovarian cancer are a pressing need. Extracellular vesicles (EVs), that include exosomes provide hope in both diagnostic and therapeutic aspects. They are natural lipid nanovesicles secreted by all cell types and carry molecules that reflect the status of the parent cell. This facilitates their potential use as biomarkers for an early diagnosis. Additionally, EVs can be loaded with exogenous cargo, and have features such as high stability and favorable pharmacokinetic properties. This makes them ideal for tumor-targeted delivery of biological moieties. The International Society of Extracellular Vesicles (ISEV) based on the Minimal Information for Studies on Extracellular Vesicles (MISEV) recommends the usage of the term "small extracellular vesicles (sEVs)" that includes exosomes for particles that are 30-200 nm in size. However, majority of the studies reported in the literature and relevant to this review have used the term "exosomes". Therefore, this review will use the term "exosomes" interchangeably with sEVs for consistency with the literature and avoid confusion to the readers. This review, initially summarizes the different isolation and detection techniques developed to study ovarian cancer-derived exosomes and the potential use of these exosomes as biomarkers for the early diagnosis of this devastating disease. It addresses the role of exosome contents in the pathogenesis of ovarian cancer, discusses strategies to limit exosome-mediated ovarian cancer progression, and provides options to use exosomes for tumor-targeted therapy in ovarian cancer. Finally, it states future research directions and recommends essential research needed to successfully transition exosomes from the laboratory to the gynecologic-oncology clinic.
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Affiliation(s)
- Dhaval Bhavsar
- Department of Pathology, University of Oklahoma Health Sciences Center, 975 NE, 10th Street, Oklahoma City, OK, 73104, USA
- OU Health Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE, 10th Street, Oklahoma City, OK, 73104, USA
| | - Rajeswari Raguraman
- Department of Pathology, University of Oklahoma Health Sciences Center, 975 NE, 10th Street, Oklahoma City, OK, 73104, USA
- OU Health Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE, 10th Street, Oklahoma City, OK, 73104, USA
| | - Dongin Kim
- Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, 1110 N, Stonewall Ave, Oklahoma City, OK, 73104, USA
- OU Health Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE, 10th Street, Oklahoma City, OK, 73104, USA
| | - Xiaoyu Ren
- Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, 1110 N, Stonewall Ave, Oklahoma City, OK, 73104, USA
| | - Anupama Munshi
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, 975 NE, 10th Street, Oklahoma City, OK, 73104, USA
- OU Health Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE, 10th Street, Oklahoma City, OK, 73104, USA
| | - Kathleen Moore
- Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, 800 NE, 10th Street, Oklahoma City, OK, 73104, USA
- OU Health Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE, 10th Street, Oklahoma City, OK, 73104, USA
| | - Vassilios Sikavitsas
- OU Health Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE, 10th Street, Oklahoma City, OK, 73104, USA
- Department of Chemical, Biological and Materials Engineering, Oklahoma University, Norman, OK, 73019, USA
| | - Rajagopal Ramesh
- Department of Pathology, University of Oklahoma Health Sciences Center, 975 NE, 10th Street, Oklahoma City, OK, 73104, USA.
- OU Health Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE, 10th Street, Oklahoma City, OK, 73104, USA.
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Shi X, Zhao X, Xue J, Jia E. Extracellular vesicle biomarkers in circulation for colorectal cancer detection: a systematic review and meta-analysis. BMC Cancer 2024; 24:623. [PMID: 38778252 PMCID: PMC11110411 DOI: 10.1186/s12885-024-12312-8] [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: 09/06/2023] [Accepted: 04/25/2024] [Indexed: 05/25/2024] Open
Abstract
We provided an overview which evaluated the diagnostic performance of circulation EV biomarkers for CRC from PubMed, Medline, and Web of Science until 21 August 2022.Weidentified 48 studies that involved 7727 participants and evaluated 162 plasma/serum individual EV biomarkers including 117 RNAs and 45 proteins, as well as 45 EV biomarker panels for CRC detection. 12 studies evaluated the diagnostic performance of EV biomarkers for early CRC. The summarized sensitivity, specificity, and AUC value of individual EV RNAs and EV RNA panels were 76%, 75%, 0.87 and 82%, 79% and 0.90, respectively. Meanwhile, those of individual EV proteins and EV protein panels were 85%, 84%, 0.92 and 87%, 83%, 0.92, respectively. These results indicated that EV biomarker panels revealed superior diagnostic performance than the corresponding individual biomarkers. In early CRC, EV biomarkers showed available diagnostic value with the sensitivity, specificity, and AUC value of 80%, 75%, and 0.89.In subgroup analyses, EV miRNAs and LncRNAs held similar diagnostic value with the sensitivity, specificity and AUC value of 75%, 78%, 0.90 and 79%, 72%, 0.83, which was highly consistent with the whole EV RNAs. Significantly, the diagnostic values of EV miRNAs in plasma were marginally higher than those based on serum. In detail, the sensitivity, specificity, and AUC values were 79%, 81%, and 0.92 in plasma, as well as 74%, 77%, and 0.88 in serum, respectively. Therefore, circulation EV biomarkers could be considered as a promising biomarker for the early detection of CRC.
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Affiliation(s)
- Xianquan Shi
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xinyu Zhao
- Clinical Epidemiology & EBM Unit, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jinru Xue
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
| | - Erna Jia
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China.
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Xiao D, Xiong M, Wang X, Lyu M, Sun H, Cui Y, Chen C, Jiang Z, Sun F. Regulation of the Function and Expression of EpCAM. Biomedicines 2024; 12:1129. [PMID: 38791091 PMCID: PMC11117676 DOI: 10.3390/biomedicines12051129] [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: 04/09/2024] [Revised: 05/11/2024] [Accepted: 05/14/2024] [Indexed: 05/26/2024] Open
Abstract
The epithelial cell adhesion molecule (EpCAM) is a single transmembrane protein on the cell surface. Given its strong expression on epithelial cells and epithelial cell-derived tumors, EpCAM has been identified as a biomarker for circulating tumor cells (CTCs) and exosomes and a target for cancer therapy. As a cell adhesion molecule, EpCAM has a crystal structure that indicates that it forms a cis-dimer first and then probably a trans-tetramer to mediate intercellular adhesion. Through regulated intramembrane proteolysis (RIP), EpCAM and its proteolytic fragments are also able to regulate multiple signaling pathways, Wnt signaling in particular. Although great progress has been made, increasingly more findings have revealed the context-specific expression and function patterns of EpCAM and their regulation processes, which necessitates further studies to determine the structure, function, and expression of EpCAM under both physiological and pathological conditions, broadening its application in basic and translational cancer research.
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Affiliation(s)
- Di Xiao
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China; (D.X.); (M.X.); (X.W.); (M.L.); (H.S.); (Y.C.)
- Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430081, China
| | - Mingrui Xiong
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China; (D.X.); (M.X.); (X.W.); (M.L.); (H.S.); (Y.C.)
- Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430081, China
| | - Xin Wang
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China; (D.X.); (M.X.); (X.W.); (M.L.); (H.S.); (Y.C.)
- Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430081, China
| | - Mengqing Lyu
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China; (D.X.); (M.X.); (X.W.); (M.L.); (H.S.); (Y.C.)
- Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430081, China
| | - Hanxiang Sun
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China; (D.X.); (M.X.); (X.W.); (M.L.); (H.S.); (Y.C.)
- Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430081, China
| | - Yeting Cui
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China; (D.X.); (M.X.); (X.W.); (M.L.); (H.S.); (Y.C.)
- Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430081, China
| | - Chen Chen
- Tumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China;
| | - Ziyu Jiang
- Tumor Precision Diagnosis and Treatment Technology and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China;
| | - Fan Sun
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China; (D.X.); (M.X.); (X.W.); (M.L.); (H.S.); (Y.C.)
- Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan 430081, China
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Romanò S, Nele V, Campani V, De Rosa G, Cinti S. A comprehensive guide to extract information from extracellular vesicles: a tutorial review towards novel analytical developments. Anal Chim Acta 2024; 1302:342473. [PMID: 38580402 DOI: 10.1016/j.aca.2024.342473] [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: 01/03/2024] [Revised: 03/11/2024] [Accepted: 03/12/2024] [Indexed: 04/07/2024]
Abstract
In the medical field, extracellular vesicles (EVs) are gaining importance as they act as cells mediators. These are phospholipid bilayer vesicles and contain crucial biochemical information about their mother cells being carrier of different biomolecules such as small molecules, proteins, lipids, and nucleic acids. After release into the extracellular matrix, they enter the systemic circulation and can be found in all human biofluids. Since EVs reflect the state of the cell of origin, there is exponential attention as potential source of new circulating biomarkers for liquid biopsy. The use of EVs in clinical practice faces several challenges that need to be addressed: these include the standardization of lysis protocols, the availability of low-cost reagents and the development of analytical tools capable of detecting biomarkers. The process of lysis is a crucial step that can impact all subsequent analyses, towards the development of novel analytical strategies. To aid researchers to support the evolution of measurement science technology, this tutorial review evaluates and discuss the most commonly protocols used to characterize the contents of EVs, including their advantages and disadvantages in terms of experimental procedures, time and equipment. The purpose of this tutorial review is to offer practical guide to researchers which are intended to develop novel analytical approaches. Some of the most significant applications are considered, highlighting their main characteristics divided per mechanism of action. Finally, comprehensive tables which provide an overview at a glance are provided to readers.
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Affiliation(s)
- Sabrina Romanò
- Department of Pharmacy, University of Naples Federico II, Italy.
| | - Valeria Nele
- Department of Pharmacy, University of Naples Federico II, Italy
| | | | | | - Stefano Cinti
- Department of Pharmacy, University of Naples Federico II, Italy.
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Bozoğlu ST, Cömert HSY, Şalcı G, Alver A, Saygın İ, Sağlam N, Erdem Ş, İmamoğlu M, Sarıhan H. Evaluation of the effectiveness of mother milk exosomes in the experimental corrosive esophagitis model. Pediatr Surg Int 2024; 40:118. [PMID: 38698156 DOI: 10.1007/s00383-024-05701-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/15/2024] [Indexed: 05/05/2024]
Abstract
PURPOSE We aimed to examine the effectiveness of mother milk exosomes in treating corrosive esophageal burns. MATERIALS AND METHODS 32 rats were separated into four equal groups and weighed individually before the procedure. A corrosive esophageal burn model was created with 12.5% sodium hydroxide by a 3F Fogarty catheter. Group 1 did not apply any process or treatment, Group 2 was burned, and no treatment was performed. Group 3 was burned, and then 0.5 cc/day of mother milk exosome extract was given. Group 4 was not applied any process, and 0.5 cc/day mother milk exosome extract was given. All rats were weighed again and sacrificed. Biopsy samples were sent to the pathology laboratory for histopathological examination (in terms of inflammation, fibrosis, and necrosis).Kindly check and confrm all email ids.The e-mail addresses and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. RESULTS A significant difference was found in the results of inflammation and fibrosis. There was a meaningful difference in fibrosis between the 2nd and 3rd groups. There was weight gain in groups 1, 3 and 4. Statistical evaluations for each group were significant. CONCLUSION It was observed that breast milk exosomes may be effective in inflammation and fibrosis formation in treating corrosive esophageal burns. This suggested that breast milk exosomes reduce stricture formation due to esophageal corrosion.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [specify authors given name] Last name [specify authors last name]. Also, kindly confirm the details in the metadata are correct.The names and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. Also we confirm the details in the metadata.
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Affiliation(s)
| | | | - Gül Şalcı
- Karadeniz Technical University, Trabzon, Turkey
| | - Ahmet Alver
- Karadeniz Technical University, Trabzon, Turkey
| | | | | | - Şeniz Erdem
- Karadeniz Technical University, Trabzon, Turkey
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Agnihotram R, Dhar R, Dhar D, Purushothaman K, Narasimhan AK, Devi A. Fusion of Exosomes and Nanotechnology: Cutting-Edge Cancer Theranostics. ACS APPLIED NANO MATERIALS 2024; 7:8489-8506. [DOI: 10.1021/acsanm.4c01033] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Affiliation(s)
- Rohan Agnihotram
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu-603203, India
| | - Rajib Dhar
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu-603203, India
| | - Debolina Dhar
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu-603203, India
| | - Kaavya Purushothaman
- Department of Biomedical Engineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu-603203, India
| | - Ashwin Kumar Narasimhan
- Department of Biomedical Engineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu-603203, India
| | - Arikketh Devi
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu-603203, India
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Javed A, Kong N, Mathesh M, Duan W, Yang W. Nanoarchitectonics-based electrochemical aptasensors for highly efficient exosome detection. SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS 2024; 25:2345041. [PMID: 38742153 PMCID: PMC11089931 DOI: 10.1080/14686996.2024.2345041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 04/15/2024] [Indexed: 05/16/2024]
Abstract
Exosomes, a type of extracellular vesicles, have attracted considerable attention due to their ability to provide valuable insights into the pathophysiological microenvironment of the cells from which they originate. This characteristic implicates their potential use as diagnostic disease biomarkers clinically, including cancer, infectious diseases, neurodegenerative disorders, and cardiovascular diseases. Aptasensors, which are electrochemical aptamers based biosensing devices, have emerged as a new class of powerful detection technology to conventional methods like ELISA and Western analysis, primarily because of their capability for high-performance bioanalysis. This review covers the current research landscape on the detection of exosomes utilizing nanoarchitectonics strategy for the development of electrochemical aptasensors. Strategies involving signal amplification and biofouling prevention are discussed, with an emphasis on nanoarchitectonics-based bio-interfaces, showcasing their potential to enhance sensitivity and selectivity through optimal conduction and mass transport properties. The ongoing challenges to broaden the clinical applications of these biosensors are also highlighted.
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Affiliation(s)
- Aisha Javed
- School of Life and Environmental Science, Centre for Sustainable Bioproducts, Deakin University, Geelong, VIC, Australia
| | - Na Kong
- School of Life and Environmental Science, Centre for Sustainable Bioproducts, Deakin University, Geelong, VIC, Australia
| | - Motilal Mathesh
- School of Life and Environmental Science, Centre for Sustainable Bioproducts, Deakin University, Geelong, VIC, Australia
| | - Wei Duan
- School of Medicine, Faculty of Health, Deakin University, Geelong, VIC, Australia
| | - Wenrong Yang
- School of Life and Environmental Science, Centre for Sustainable Bioproducts, Deakin University, Geelong, VIC, Australia
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Zhong W, Zhao X, Zhang X, Xu Y, Liu M, Yang X, Jiang Y, Shen X. Advancements and trends in exosome research in lung cancer from a bibliometric analysis (2004-2023). Front Oncol 2024; 14:1358101. [PMID: 38690166 PMCID: PMC11058220 DOI: 10.3389/fonc.2024.1358101] [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: 12/19/2023] [Accepted: 04/04/2024] [Indexed: 05/02/2024] Open
Abstract
Background Lung cancer, characterized by its high morbidity and lethality, necessitates thorough research to enhance our understanding of its pathogenesis and discover novel therapeutic approaches. Recent studies increasingly demonstrate that lung cancer cells can modulate the tumor microenvironment, promoting tumor growth, and metastasis through the release of exosomes. Exosomes are small vesicles secreted by cells and contain a variety of bioactive molecules such as proteins, nucleic acids, and metabolites. This paper presents a comprehensive review of exosome research in lung cancer and its progress through bibliometric analysis. Methods Publications related to exosomes in lung cancer patients were systematically searched on the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using VOSviwers, CiteSpace, and the R package "Bibliometrics". Publications were quantitatively analyzed using Microsoft Office Excel 2019. The language of publication was restricted to "English" and the search strategy employed TS=(exosomes or exosomes or exosomes) and TS=(lung cancer). The search period commenced on January 1, 2004, and concluded on November 12, 2023, at noon. The selected literature types included Articles and Reviews. Results The study encompassed 1699 papers from 521 journals across 71 countries and 2105 institutions. Analysis revealed a consistent upward trend in lung cancer exosome research over the years, with a notable surge in recent times. This surge indicates a growing interest and depth of inquiry into lung cancer exosomes. Major research institutions in China and the United States, including Nanjing Medical University, Shanghai Jiao Tong University, Chinese Academy Of Sciences, and Utmd Anderson Cancer Center, emerged as crucial research hubs. The annual publication count in this field witnessed a continuous rise, particularly in recent years. Key terms such as lung cancer, non-small cell lung cancer (NSCLC), microvesicles, intercellular communication, exosomal miRNAs, and oncology dominated the research landscape. Fields like cell biology, biochemistry, biotechnology, and oncology exhibited close relation with this research. Clotilde Théry emerged as the most cited author in the field, underlining her significant contributions. These results demonstrate the broad impact of exosome research in lung cancer, with key terms covering not only disease-specific aspects such as lung cancer and NSCLC but also basic biological concepts like microvesicles and intercellular communication. Explorations into exosomal microRNAs and oncology have opened new avenues for lung cancer exosome research. In summary, lung cancer exosome research is poised to continue receiving attention, potentially leading to breakthroughs in treatment and prevention. Conclusion Publications on lung cancer exosomes show a rising trend year by year, with China and the United States ranking first and second in terms of the number of publications. However, there is insufficient academic learning cooperation and exchanges between the two sides, and Chinese universities account for a large proportion of research institutions in this field. Jing Li is the most productive author, Clotilde Théry is the most co-cited author, and Cancers is the journal with the highest number of publications. The current focus in the field of lung cancer exosomes is on biomarkers, liquid biopsies, immunotherapy, and tumor microenvironment.
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Affiliation(s)
- Wen Zhong
- Department of Geriatrics, Lianyungang Hospital Affiliated to Jiangsu University, Lianyungang, China
| | - Xiaofei Zhao
- Department of Geriatrics, Lianyungang Hospital Affiliated to Jiangsu University, Lianyungang, China
| | - Xiabiao Zhang
- Department of Neurosurgery, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Yiwen Xu
- Department of Infectious Disease, The First Affiliated Hospital of Ningbo University, Ningbo, China
| | - Mengqian Liu
- Department of Geriatrics, Lianyungang Hospital Affiliated to Jiangsu University, Lianyungang, China
| | - Xiaoyun Yang
- Department of Geriatrics, Lianyungang Hospital Affiliated to Jiangsu University, Lianyungang, China
| | - Yi Jiang
- Department of Geriatrics, Lianyungang Hospital Affiliated to Bengbu Medical College, Lianyungang, China
| | - Xiaozhu Shen
- Department of Geriatrics, Lianyungang Hospital Affiliated to Jiangsu University, Lianyungang, China
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Ao K, Yin M, Lyu X, Xiao Y, Chen X, Zhong S, Wen X, Yuan J, Ye M, Zhang J, Li X, Hao Y, Guo X. METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer. Cancer Lett 2024; 587:216658. [PMID: 38253218 DOI: 10.1016/j.canlet.2024.216658] [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: 09/25/2023] [Revised: 01/16/2024] [Accepted: 01/16/2024] [Indexed: 01/24/2024]
Abstract
The role of RNA methyltransferase 3 (METTL3) in tumor progression when tethered to aberrantly expressed oncogenes remains unknown. In especial, the correlation between cervical cancer (CCa)-derived exosomes and m6A methylation in malignant traits of cervical epithelium is currently elusive. Mortalin expression was found to be up-regulated in plasma exosomes isolated from CCa patients. Furthermore, mortalin gained increased mRNA stability and enhanced translation efficiency via the m6A methylation in the HSPA9 mRNA 3'UTR, which was catalysed by METTL3 in CCa cells. Exosomal mortalin overexpression significantly promoted the proliferation, migration and invasion of CCa both in vitro and in vivo. Additionally, exosome-encapsulated mortalin suppressed cellular senescence and facilitated malignant transformation by blocking nuclear transport of p53, thereby preventing the p53-Gadd45A interaction and resulting in inactivation of p53. Our studies demonstrated the significant role of METTL3 mediated exosomal mortalin in malignant transformation and cellular senescence suppression of CCa. Exosomal mortalin could clinically serve as a potential early-diagnosis biomarker and therapeutic target for CCa given its abundance and propensity to be found.
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Affiliation(s)
- Keyi Ao
- Department of Science and Innovation, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518100, PR China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China.
| | - Minuo Yin
- Department of Obstetrics and Gynecology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518100, PR China.
| | - Xiaoming Lyu
- Department of Laboratory Medicine, The Third Affiliated Hospital, Southern Medical University, Guangdong, 510515, PR China.
| | - Yue Xiao
- Department of Science and Innovation, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518100, PR China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China.
| | - Xiaona Chen
- Department of Science and Innovation, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518100, PR China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China.
| | - Sheng Zhong
- Department of Science and Innovation, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518100, PR China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China.
| | - Xiuli Wen
- Department of Ultrasound, South China Hospital of Shenzhen University, Shenzhen, Guangdong, 518100, PR China.
| | - Jianli Yuan
- Department of Gynecology, Affiliated Cancer Hospital, Xinjiang Medical University, Urumqi, Xiangjiang, 830000, PR China.
| | - Ming Ye
- Department of Pathology, Afiliated Cancer Hospital, Xinjiang Medical University, Urumqi, Xiangjiang, 830000, PR China.
| | - Jiaming Zhang
- Department of Obstetrics and Gynecology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518100, PR China.
| | - Xin Li
- Department of Science and Innovation, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518100, PR China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China; Shenzhen Key Laboratory of Viral Oncology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518100, PR China.
| | - Yi Hao
- Department of Ultrasound, South China Hospital of Shenzhen University, Shenzhen, Guangdong, 518100, PR China.
| | - Xia Guo
- Department of Science and Innovation, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518100, PR China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, PR China; Shenzhen Key Laboratory of Viral Oncology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, 518100, PR China.
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Bhandari K, Ding WQ. Protein Arginine Methyltransferases in Pancreatic Ductal Adenocarcinoma: New Molecular Targets for Therapy. Int J Mol Sci 2024; 25:3958. [PMID: 38612768 PMCID: PMC11011826 DOI: 10.3390/ijms25073958] [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: 02/29/2024] [Revised: 03/28/2024] [Accepted: 03/30/2024] [Indexed: 04/14/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant disease with a low 5-year overall survival rate. It is the third-leading cause of cancer-related deaths in the United States. The lack of robust therapeutics, absence of effective biomarkers for early detection, and aggressive nature of the tumor contribute to the high mortality rate of PDAC. Notably, the outcomes of recent immunotherapy and targeted therapy against PDAC remain unsatisfactory, indicating the need for novel therapeutic strategies. One of the newly described molecular features of PDAC is the altered expression of protein arginine methyltransferases (PRMTs). PRMTs are a group of enzymes known to methylate arginine residues in both histone and non-histone proteins, thereby mediating cellular homeostasis in biological systems. Some of the PRMT enzymes are known to be overexpressed in PDAC that promotes tumor progression and chemo-resistance via regulating gene transcription, cellular metabolic processes, RNA metabolism, and epithelial mesenchymal transition (EMT). Small-molecule inhibitors of PRMTs are currently under clinical trials and can potentially become a new generation of anti-cancer drugs. This review aims to provide an overview of the current understanding of PRMTs in PDAC, focusing on their pathological roles and their potential as new therapeutic targets.
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Affiliation(s)
| | - Wei-Qun Ding
- Department of Pathology, University of Oklahoma Health Sciences Center, BMSB401A, 940 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA;
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Levin G, Oranim N, Meyer R. Top-cited articles in the gynecologic oncology. Arch Gynecol Obstet 2024; 309:1691-1693. [PMID: 38047936 DOI: 10.1007/s00404-023-07325-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 11/27/2023] [Indexed: 12/05/2023]
Affiliation(s)
- Gabriel Levin
- Faculty of Medicine, The Department of Gynecologic Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, 91120, Jerusalem, Israel.
- Lady Davis Institute for Cancer Research, Jewish General Hospital, McGill University, Montreal, Canada.
| | - Noa Oranim
- Chaim Sheba Medical Center, Ramat-Gan, Israel
| | - Raanan Meyer
- Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Ramat-Gan, Israel
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Cedar-Sinai Medical Center, Los Angeles, USA
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35
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Chen J, He F, Peng H, Guo J. The underlying mechanism and targeted therapy strategy of miRNAs cross-regulating EMT process through multiple signaling pathways in hepatocellular carcinoma. Front Mol Biosci 2024; 11:1378386. [PMID: 38584703 PMCID: PMC10995332 DOI: 10.3389/fmolb.2024.1378386] [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: 01/29/2024] [Accepted: 03/04/2024] [Indexed: 04/09/2024] Open
Abstract
The consistent notion holds that hepatocellular carcinoma (HCC) initiation, progression, and clinical treatment failure treatment failure are affected by the accumulation of various genetic and epigenetic alterations. MicroRNAs (miRNAs) play an irreplaceable role in a variety of physiological and pathological states. meanwhile, epithelial-mesenchymal transition (EMT) is a crucial biological process that controls the development of HCC. miRNAs regulate the intermediation state of EMTor mesenchymal-epithelial transition (MTE)thereby regulating HCC progression. Notably, miRNAs regulate key HCC-related molecular pathways, including the Wnt/β-catenin pathway, PTEN/PI3K/AKT pathway, TGF-β pathway, and RAS/MAPK pathway. Therefore, we comprehensively reviewed how miRNAs produce EMT effects by multiple signaling pathways and their potential significance in the pathogenesis and treatment response of HCC. emphasizing their molecular pathways and progression in HCC initiation. Additionally, we also pay attention to regulatory mechanisms that are partially independent of signaling pathways. Finally, we summarize and propose miRNA-targeted therapy and diagnosis and defense strategies forHCC. The identification of the mechanism leading to the activation of EMT programs during HCC disease processes also provides a new protocol for the plasticity of distinct cellular phenotypes and possible therapeutic interventions. Consequently, we summarize the latest progress in this direction, with a promising path for further insight into this fast-moving field.
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Affiliation(s)
- Juan Chen
- Department of Pathology, Bishan Hospital of Chongqing Medical University, Chongqing, China
| | - Fuguo He
- Department of Pathology, Bishan Hospital of Chongqing Medical University, Chongqing, China
| | - Hong Peng
- Department of Gastroenterology, Bishan Hospital of Chongqing Medical University, Chongqing, China
| | - Jinjun Guo
- Department of Gastroenterology, Bishan Hospital of Chongqing Medical University, Chongqing, China
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36
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Salehi M, Kamali MJ, Arab D, Safaeian N, Ashuori Z, Maddahi M, Latifi N, Jahromi AM. Exosomal microRNAs in regulation of tumor cells resistance to apoptosis. Biochem Biophys Rep 2024; 37:101644. [PMID: 38298209 PMCID: PMC10827597 DOI: 10.1016/j.bbrep.2024.101644] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 01/06/2024] [Accepted: 01/09/2024] [Indexed: 02/02/2024] Open
Abstract
Exosomes are a type of extracellular vesicle that contains bioactive molecules that can be secreted by most cells. Nevertheless, the content of these cells differs depending on the cell from which they originate. The exosome plays a crucial role in modulating intercellular communication by conveying molecular messages to neighboring or distant cells. Cancer-derived exosomes can transfer several types of molecules into the tumor microenvironment, including high levels of microRNA (miRNA). These miRNAs significantly affect cell proliferation, angiogenesis, apoptosis resistance, metastasis, and immune evasion. Increasing evidence indicates that exosomal miRNAs (exomiRs) are crucial to regulating cancer resistance to apoptosis. In cancer cells, exomiRs orchestrate communication channels between them and their surrounding microenvironment, modulating gene expression and controlling apoptosis signaling pathways. This review presents an outline of present-day knowledge of the mechanisms that affect target cells and drive cancer resistance to apoptosis. Also, our study looks at the regulatory role of exomiRs in mediating intercellular communication between tumor cells and surrounding microenvironmental cells, specifically stromal and immune cells, to evade therapy-induced apoptosis.
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Affiliation(s)
- Mohammad Salehi
- Department of Medical Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
- Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mohammad Javad Kamali
- Department of Medical Genetics, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Daniyal Arab
- Department of Human Genetics, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Naghme Safaeian
- Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Zahra Ashuori
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Moein Maddahi
- Faculty of Dentistry, Yeditepe University, Istanbul, Turkey
| | - Narges Latifi
- Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Iran
| | - Amir Moein Jahromi
- School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
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37
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Ghose A, McCann L, Makker S, Mukherjee U, Gullapalli SVN, Erekkath J, Shih S, Mahajan I, Sanchez E, Uccello M, Moschetta M, Adeleke S, Boussios S. Diagnostic biomarkers in ovarian cancer: advances beyond CA125 and HE4. Ther Adv Med Oncol 2024; 16:17588359241233225. [PMID: 38435431 PMCID: PMC10908239 DOI: 10.1177/17588359241233225] [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: 04/05/2023] [Accepted: 01/26/2024] [Indexed: 03/05/2024] Open
Abstract
Ovarian cancer (OC) is the most lethal gynaecologic malignancy, attributed to its insidious growth, non-specific symptoms and late presentation. Unfortunately, current screening modalities are inadequate at detecting OC and many lack the appropriate specificity and sensitivity that is desired from a screening test. Nearly 70% of cases are diagnosed at stage III or IV with poor 5-year overall survival. Therefore, the development of a sensitive and specific biomarker for early diagnosis and screening for OC is of utmost importance. Currently, diagnosis is guided by CA125, the patient's menopausal status and imaging features on ultrasound scan. However, emerging evidence suggests that a combination of CA125 and HE4 (another serum biomarker) and patient characteristics in a multivariate index assay may provide a higher specificity and sensitivity than either CA125 and HE4 alone in the early detection of OC. Other attempts at combining various serum biomarkers into one multivariate index assay such as OVA1, ROMA and Overa have all shown promise. However, significant barriers exist before these biomarkers can be implemented in clinical practice. This article aims to provide an up-to-date review of potential biomarkers for screening and early diagnosis of OC which may have the potential to transform its diagnostic landscape.
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Affiliation(s)
- Aruni Ghose
- Department of Medical Oncology, Barts Cancer Centre, St. Bartholomew’s Hospital, Barts Health NHS Trust, London, UK
- Department of General Medicine, Newham University Hospital, Barts Health NHS Trust, London, UK
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham, UK
- Department of Medical Oncology, Mount Vernon Cancer Centre, East and North Hertfordshire NHS Trust, London, UK
| | - Lucy McCann
- Department of General Medicine, Newham University Hospital, Barts Health NHS Trust, London, UK
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
| | - Shania Makker
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- University College London Cancer Institute, London, UK
| | - Uma Mukherjee
- Department of Medical Oncology, Barts Cancer Centre, St. Bartholomew’s Hospital, Barts Health NHS Trust, London, UK
- University College London Cancer Institute, London, UK
| | | | - Jayaraj Erekkath
- Department of Medical Oncology, Northern Ireland Cancer Centre, Belfast City Hospital, Belfast Health and Social Care Trust, Belfast, UK
| | - Stephanie Shih
- Department of General Medicine, Newham University Hospital, Barts Health NHS Trust, London, UK
| | - Ishika Mahajan
- Department of Acute Medicine, Lincoln County Hospital, United Lincolnshire Hospitals NHS Trust, Lincoln, Lincolnshire, UK
- Department of Medical Oncology, Apollo Cancer Centre, Chennai, Tamil Nadu, India
| | - Elisabet Sanchez
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham, UK
| | - Mario Uccello
- Department of Medical Oncology, Southampton General Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | | | - Sola Adeleke
- Department of Clinical Oncology, Cancer Centre at Guy’s, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK
- Faculty of Life Sciences and Medicine, School of Cancer and Pharmaceutical Sciences, King’s College London, Guy’s Campus, London, WC2R 2LS, UK
| | - Stergios Boussios
- Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham, UK
- Faculty of Life Sciences and Medicine, School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK
- Kent and Medway Medical School, University of Kent, Canterbury, UK
- AELIA Organization, Thermi, Thessaloniki, Greece
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38
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Wang Z, Wang Q, Qin F, Chen J. Exosomes: a promising avenue for cancer diagnosis beyond treatment. Front Cell Dev Biol 2024; 12:1344705. [PMID: 38419843 PMCID: PMC10900531 DOI: 10.3389/fcell.2024.1344705] [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: 11/26/2023] [Accepted: 01/31/2024] [Indexed: 03/02/2024] Open
Abstract
Exosomes, extracellular vesicles secreted by cells, have garnered significant attention in recent years for their remarkable therapeutic potential. These nanoscale carriers can be harnessed for the targeted delivery of therapeutic agents, such as pharmaceuticals, proteins, and nucleic acids, across biological barriers. This versatile attribute of exosomes is a promising modality for precision medicine applications, notably in the realm of cancer therapy. However, despite their substantial therapeutic potential, exosomes still confront challenges tied to standardization and scalability that impede their practice in clinical applications. Moreover, heterogeneity in isolation methodologies and limited cargo loading mechanisms pose obstacles to ensuring consistent outcomes, thereby constraining their therapeutic utility. In contrast, exosomes exhibit a distinct advantage in cancer diagnosis, as they harbor specific signatures reflective of the tumor's genetic and proteomic profile. This characteristic endows them with the potential to serve as valuable liquid biopsies for non-invasive and real-time monitoring, making possible early cancer detection for the development of personalized treatment strategies. In this review, we provide an extensive evaluation of the advancements in exosome research, critically examining their advantages and limitations in the context of cancer therapy and early diagnosis. Furthermore, we present a curated overview of the most recent technological innovations utilizing exosomes, with a focus on enhancing the efficacy of early cancer detection.
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Affiliation(s)
- Zhu Wang
- Breast Center, West China Hospital, Sichuan University, Chengdu, China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Institute for Breast Health Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Qianqian Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Feng Qin
- School of Basic Medicine, Dali University, Dali, Yunnan, China
| | - Jie Chen
- Breast Center, West China Hospital, Sichuan University, Chengdu, China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Institute for Breast Health Medicine, West China Hospital, Sichuan University, Chengdu, China
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39
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Han SB, Lee SS. Simultaneous Detection of Exosomal microRNAs Isolated from Cancer Cells Using Surface Acoustic Wave Sensor Array with High Sensitivity and Reproducibility. MICROMACHINES 2024; 15:249. [PMID: 38398977 PMCID: PMC10892992 DOI: 10.3390/mi15020249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 02/02/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024]
Abstract
We present a surface acoustic wave (SAW) sensor array for microRNA (miRNA) detection that utilizes photocatalytic silver staining on titanium dioxide (TiO2) nanoparticles as a signal enhancement technique for high sensitivity with an internal reference sensor for high reproducibility. A sandwich hybridization was performed on working sensors of the SAW sensor array that could simultaneously capture and detect three miRNAs (miRNA-21, miRNA-106b, and miRNA-155) known to be upregulated in cancer. Sensor responses due to signal amplification varied depending on the concentration of synthetic miRNAs. It was confirmed that normalization (a ratio of working sensor response to reference sensor response) screened out background interferences by manipulating data and minimized non-uniformity in the photocatalytic silver staining step by suppressing disturbances to both working sensor signal and reference sensor signal. Finally, we were able to successfully detect target miRNAs in cancer cell-derived exosomal miRNAs with performance comparable to the detection of synthetic miRNAs.
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Affiliation(s)
| | - Soo Suk Lee
- Department of Pharmaceutical Engineering, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si 31538, Chungcheongnam-do, Republic of Korea;
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40
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Bhandari K, Kong JS, Morris K, Xu C, Ding WQ. Protein Arginine Methylation Patterns in Plasma Small Extracellular Vesicles Are Altered in Patients with Early-Stage Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2024; 16:654. [PMID: 38339405 PMCID: PMC10854811 DOI: 10.3390/cancers16030654] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 01/30/2024] [Accepted: 02/01/2024] [Indexed: 02/12/2024] Open
Abstract
Small extracellular vesicles (sEVs) contain lipids, proteins and nucleic acids, which often resemble their cells of origin. Therefore, plasma sEVs are considered valuable resources for cancer biomarker development. However, previous efforts have been largely focused on the level of proteins and miRNAs in plasma sEVs, and the post-translational modifications of sEV proteins, such as arginine methylation, have not been explored. Protein arginine methylation, a relatively stable post-translational modification, is a newly described molecular feature of PDAC. The present study examined arginine methylation patterns in plasma sEVs derived from patients with early-stage PDAC (n = 23) and matched controls. By utilizing the arginine methylation-specific antibodies for western blotting, we found that protein arginine methylation patterns in plasma sEVs are altered in patients with early-stage PDAC. Specifically, we observed a reduction in the level of symmetric dimethyl arginine (SDMA) in plasma sEV proteins derived from patients with early- and late-stage PDAC. Importantly, immunoprecipitation followed by proteomics analysis identified a number of arginine-methylated proteins exclusively present in plasma sEVs derived from patients with early-stage PDAC. These results indicate that arginine methylation patterns in plasma sEVs are potential indicators of PDAC, a new concept meriting further investigation.
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Affiliation(s)
- Kritisha Bhandari
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (K.B.); (J.S.K.)
| | - Jeng Shi Kong
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (K.B.); (J.S.K.)
| | - Katherine Morris
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Chao Xu
- Department of Biostatistics & Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA;
| | - Wei-Qun Ding
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (K.B.); (J.S.K.)
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41
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Miron RJ, Zhang Y. Understanding exosomes: Part 1-Characterization, quantification and isolation techniques. Periodontol 2000 2024; 94:231-256. [PMID: 37740431 DOI: 10.1111/prd.12520] [Citation(s) in RCA: 24] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 07/21/2023] [Accepted: 07/25/2023] [Indexed: 09/24/2023]
Abstract
Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with a diameter in the range of 30-150 nm. Their use has gained great momentum recently due to their ability to be utilized as diagnostic tools with a vast array of therapeutic applications. Over 5000 publications are currently being published yearly on this topic, and this number is only expected to dramatically increase as novel therapeutic strategies continue to be investigated. This review article first focuses on understanding exosomes, including their cellular origin, biogenesis, function, and characterization. Thereafter, overviews of the quantification methods and isolation techniques are given with discussion over their potential use as novel therapeutics in regenerative medicine.
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Affiliation(s)
- Richard J Miron
- Department of Periodontology, University of Bern, Bern, Switzerland
| | - Yufeng Zhang
- Department of Oral Implantology, University of Wuhan, Wuhan, China
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42
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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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43
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Wilczyński J, Paradowska E, Wilczyński M. High-Grade Serous Ovarian Cancer-A Risk Factor Puzzle and Screening Fugitive. Biomedicines 2024; 12:229. [PMID: 38275400 PMCID: PMC10813374 DOI: 10.3390/biomedicines12010229] [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: 11/12/2023] [Revised: 01/14/2024] [Accepted: 01/17/2024] [Indexed: 01/27/2024] Open
Abstract
High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of the female genital tract. Despite extensive studies and the identification of some precursor lesions like serous tubal intraepithelial cancer (STIC) or the deviated mutational status of the patients (BRCA germinal mutation), the pathophysiology of HGSOC and the existence of particular risk factors is still a puzzle. Moreover, a lack of screening programs results in delayed diagnosis, which is accompanied by a secondary chemo-resistance of the tumor and usually results in a high recurrence rate after the primary therapy. Therefore, there is an urgent need to identify the substantial risk factors for both predisposed and low-risk populations of women, as well as to create an economically and clinically justified screening program. This paper reviews the classic and novel risk factors for HGSOC and methods of diagnosis and prediction, including serum biomarkers, the liquid biopsy of circulating tumor cells or circulating tumor DNA, epigenetic markers, exosomes, and genomic and proteomic biomarkers. The novel future complex approach to ovarian cancer diagnosis should be devised based on these findings, and the general outcome of such an approach is proposed and discussed in the paper.
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Affiliation(s)
- Jacek Wilczyński
- Department of Gynecological Surgery and Gynecological Oncology, Medical University of Lodz, 4 Kosciuszki Str., 90-419 Lodz, Poland
| | - Edyta Paradowska
- Laboratory of Virology, Institute of Medical Biology of the Polish Academy of Sciences, 106 Lodowa Str., 93-232 Lodz, Poland;
| | - Miłosz Wilczyński
- Department of Surgical, Endoscopic and Gynecological Oncology, Polish Mother’s Health Center—Research Institute, 281/289 Rzgowska Str., 93-338 Lodz, Poland;
- Department of Surgical and Endoscopic Gynecology, Medical University of Lodz, 4 Kosciuszki Str., 90-419 Lodz, Poland
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44
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Najafi S, Majidpoor J, Mortezaee K. Liquid biopsy in colorectal cancer. Clin Chim Acta 2024; 553:117674. [PMID: 38007059 DOI: 10.1016/j.cca.2023.117674] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 11/16/2023] [Accepted: 11/20/2023] [Indexed: 11/27/2023]
Abstract
Liquid biopsy refers to a set of pathological samples retrieved from non-solid sources, such as blood, cerebrospinal fluid, urine, and saliva through non-invasive or minimally invasive approaches. In the recent decades, an increasing number of studies have focused on clinical applications and improving technological investigation of liquid biopsy biosources for diagnostic goals particularly in cancer. Materials extracted from these sources and used for medical evaluations include cells like circulating tumor cells (CTCs), tumor-educated platelets (TEPs), cell-free nucleic acids released by cells, such as circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), cell-free RNA (cfRNA), and exosomes. Playing significant roles in the pathogenesis of human malignancies, analysis of these sources can provide easier access to genetic and transcriptomic information of the cancer tissue even better than the conventional tissue biopsy. Notably, they can represent the inter- and intra-tumoral heterogeneity and accordingly, liquid biopsies demonstrate strengths for improving diagnosis in early detection and screening, monitoring and follow-up after therapies, and personalization of therapeutical strategies in various types of human malignancies. In this review, we aim to discuss the roles, functions, and analysis approaches of liquid biopsy sources and their clinical implications in human malignancies with a focus on colorectal cancer.
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Affiliation(s)
- Sajad Najafi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jamal Majidpoor
- Department of Anatomy, School of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Keywan Mortezaee
- Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
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45
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Fais S, Logozzi M. The Diagnostic and Prognostic Value of Plasmatic Exosome Count in Cancer Patients and in Patients with Other Pathologies. Int J Mol Sci 2024; 25:1049. [PMID: 38256122 PMCID: PMC10816819 DOI: 10.3390/ijms25021049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/03/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024] Open
Abstract
The extent of both scientific articles and reviews on extracellular vesicles (EVs) has grown impressively over the last few decades [...].
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Affiliation(s)
- Stefano Fais
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
- ExoLab Italia, Tecnopolo d’Abruzzo, 67100 L’Aquila, Italy
| | - Mariantonia Logozzi
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
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46
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Zhang Y, Zhao J, Han L, Zhang Z, Wang C, Long W, Meng K, Wang X. Research progress of extracellular vesicles in the treatment of ovarian diseases (Review). Exp Ther Med 2024; 27:15. [PMID: 38125352 PMCID: PMC10728905 DOI: 10.3892/etm.2023.12303] [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: 04/26/2023] [Accepted: 11/02/2023] [Indexed: 12/23/2023] Open
Abstract
The ovary is an essential reproductive organ in the female organism and its development seriously affects the physical and mental health of female patients. Ovarian diseases include ovarian cancer, premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). Women should pay attention to the most effective treatments for this condition because it is one of the most prevalent gynecological illnesses at present. Extracellular vesicles (EVs), which are smaller vesicles that mediate the exchange of cellular information, include the three categories of exosomes, microvesicles and apoptotic bodies. They are able to transport proteins, RNA and other substances to adjacent or distal cells, thus allowing cellular and tissue homeostasis to be maintained. Numerous previous studies have revealed that EVs are crucial for the treatment of ovarian diseases. They are known to transport its contents to ovarian cancer cells as well as other ovarian cells such as granulosa cells, affecting the development of ovarian disease processes. Therefore, this extracellular vesicle may be involved as a target in the therapeutic process of ovarian disease and may have great potential in the treatment of ovarian disease. In the present review, the role of EVs in the development of three ovarian diseases, including ovarian cancer, POI and PCOS, was mainly summarizes. It is expected that this will provide some theoretical support for the treatment of ovarian disease.
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Affiliation(s)
- Yixin Zhang
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong 272067, P.R. China
- College of Second Clinical Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Jingyu Zhao
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong 272067, P.R. China
- College of Second Clinical Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Linqi Han
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong 272067, P.R. China
- College of Second Clinical Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Zihan Zhang
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong 272067, P.R. China
- College of Second Clinical Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Caiqin Wang
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong 272067, P.R. China
- College of Second Clinical Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Wei Long
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong 272067, P.R. China
- College of Second Clinical Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Kai Meng
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong 272067, P.R. China
- Lin He's Academician Workstation of New Medicine and Clinical Translation, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Xiaomei Wang
- College of Basic Medicine, Jining Medical University, Jining, Shandong 272067, P.R. 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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Fanale D, Corsini LR, Bono M, Randazzo U, Barraco N, Brando C, Cancelliere D, Contino S, Giurintano A, Magrin L, Pedone E, Perez A, Piraino P, Pivetti A, Giovanni ED, Russo TDB, Prestifilippo O, Gennusa V, Pantuso G, Russo A, Bazan V. Clinical relevance of exosome-derived microRNAs in Ovarian Cancer: Looking for new tumor biological fingerprints. Crit Rev Oncol Hematol 2024; 193:104220. [PMID: 38036154 DOI: 10.1016/j.critrevonc.2023.104220] [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: 08/30/2023] [Revised: 11/17/2023] [Accepted: 11/24/2023] [Indexed: 12/02/2023] Open
Abstract
Specific tumor-derived extracellular vesicles, called exosomes, are considered as potential key players in cross-talk between immune system and tumor microenvironment in several solid tumors. Different studies highlighted the clinical relevance of exosomes in ovarian cancer (OC) for their role in early diagnosis, prognosis, chemoresistance, targeted therapy. The exosomes are nanosize vesicles carrying lipids, proteins, and nucleic acids. In particular, exosomes shuttle a wide spectrum of microRNAs (miRNAs) able to induce phenotypic reprogramming of target cells, contributing to tumor progression. In this review, we will discuss the promising role of miRNAs shuttled by exosomes, called exosomal miRNAs (exo-miRNAs), as potential biomarkers for early detection, tumour progression and metastasis, prognosis, and response to therapy in OC women, in order to search for new potential biological fingerprints able to better characterize the evolution of this malignancy and provide a clinically relevant non-invasive approach useful for adopting, in future, personalized therapeutic strategies.
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Affiliation(s)
- Daniele Fanale
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Lidia Rita Corsini
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Marco Bono
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Ugo Randazzo
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Nadia Barraco
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Chiara Brando
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Daniela Cancelliere
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Silvia Contino
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Ambra Giurintano
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Luigi Magrin
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Erika Pedone
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Alessandro Perez
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Paola Piraino
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Alessia Pivetti
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Emilia Di Giovanni
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Tancredi Didier Bazan Russo
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Ornella Prestifilippo
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Vincenzo Gennusa
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Gianni Pantuso
- Division of General and Oncological Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Antonio Russo
- Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127 Palermo, Italy.
| | - Viviana Bazan
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
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49
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Liu J, Hu X, Xin W, Wang X. Exosomal Non-coding RNAs: A New Approach to Melanoma Diagnosis and Therapeutic Strategy. Curr Med Chem 2024; 31:6084-6109. [PMID: 37877505 DOI: 10.2174/0109298673267553231017053329] [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: 06/15/2023] [Revised: 09/03/2023] [Accepted: 09/22/2023] [Indexed: 10/26/2023]
Abstract
Malignant melanoma (MM) is a highly aggressive cancer with a poor prognosis. Currently, although a variety of therapies are available for treating melanoma, MM is still a serious threat to the patient's life due to numerous factors, such as the recurrence of tumors, the emergence of drug resistance, and the lack of effective therapeutic agents. Exosomes are biologically active lipid-bilayer extracellular vesicles secreted by diverse cell types that mediate intercellular signal communication. Studies found that exosomes are involved in cancer by carrying multiple bioactive molecules, including non-- coding RNAs (ncRNAs). The ncRNAs have been reported to play an important role in regulating proliferation, angiogenesis, immune regulation, invasion, metastasis, and treatment resistance of tumors. However, the functional role of exosomal ncRNAs in MM remains unknown. Therefore, this review summarizes the current state of melanoma diagnosis, treatment, and the application of exosomal ncRNAs in MM patients, which may provide new insights into the mechanisms involved in melanoma progression and serve as biomarkers for diagnosis and therapeutic targets.
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Affiliation(s)
- Jie Liu
- Department of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Xiaoping Hu
- Department of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Wenqiang Xin
- Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China, 300052
| | - Xianbin Wang
- Department of Emergency Medicine, The Second Affiliated Hospital of Baotou Medical College, Baotou 014030, China
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50
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Zhou X, Liu M, Sun L, Cao Y, Tan S, Luo G, Liu T, Yao Y, Xiao W, Wan Z, Tang J. Circulating small extracellular vesicles microRNAs plus CA-125 for treatment stratification in advanced ovarian cancer. J Transl Med 2023; 21:927. [PMID: 38129848 PMCID: PMC10740240 DOI: 10.1186/s12967-023-04774-4] [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: 06/08/2023] [Accepted: 11/28/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND No residual disease (R0 resection) after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models. METHODS RNA sequencing of circulating small extracellular vesicles (sEVs) was used to discover the differential expression microRNAs (DEMs) profile between any residual disease (R0, n = 17) and no residual disease (non-R0, n = 20) in AOC patients. We further analyzed plasma samples of AOC patients collected before surgery or neoadjuvant chemotherapy via TaqMan qRT-PCR. The combined risk model of residual disease was developed by logistic regression analysis based on the discovery-validation sets. RESULTS Using a comprehensive plasma small extracellular vesicles (sEVs) microRNAs (miRNAs) profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA and CA-125 with better performance in predicting R0 resection. Based on 360 clinical human samples, this model was constructed using least absolute shrinkage and selection operator (LASSO) and logistic regression analysis, and it has favorable calibration and discrimination ability (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (NRI = 0.471, IDI = 0.538, p < 0.001; NRI = 0.122, IDI = 0.185, p < 0.01). CONCLUSION Overall, we established a reliable, non-invasive, and objective detection method composed of circulating tumor-derived sEVs 4-miRNA plus CA-125 to preoperatively anticipate the high-risk AOC patients of residual disease to optimize clinical therapy.
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Affiliation(s)
- Xiaofang Zhou
- Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China
- Department of Oncology, Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China
| | - Mu Liu
- Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China
| | - Lijuan Sun
- Department of Gynecology and Obstetrics, The Central Hospital of Shaoyang, Shaoyang, 422000, People's Republic of China
| | - Yumei Cao
- Department of Gynecology and Obstetrics, The Central Hospital of Shaoyang, Shaoyang, 422000, People's Republic of China
| | - Shanmei Tan
- Department of Gynecology and Obstetrics, The First People's Hospital of Huaihua, The Affiliated Huaihua Hospital of University of South China, Huaihua, 418000, People's Republic of China
| | - Guangxia Luo
- Department of Gynecology and Obstetrics, The First People's Hospital of Huaihua, The Affiliated Huaihua Hospital of University of South China, Huaihua, 418000, People's Republic of China
| | - Tingting Liu
- Department of Gynecology and Obstetrics, The First People's Hospital of Changde, Changde, 415000, People's Republic of China
| | - Ying Yao
- Department of Gynecology and Obstetrics, The First People's Hospital of Yueyang, Yueyang, 414000, People's Republic of China
| | - Wangli Xiao
- Department of Gynecology and Obstetrics, The First People's Hospital of Yueyang, Yueyang, 414000, People's Republic of China
| | - Ziqing Wan
- Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China
| | - Jie Tang
- Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China.
- Department of Gynecologic Oncology, Hunan Gynecologic Cancer Research Center, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Address: 283 Tongzipo Road, Yuelu District, Changsha, 410013, People's Republic of China.
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