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Y M, L D. Gastric cancer peritoneal metastasis: a bibliometric study from 2000 to 2024 using VOSviewer software. Front Oncol 2025; 15:1489043. [PMID: 40104504 PMCID: PMC11913700 DOI: 10.3389/fonc.2025.1489043] [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: 08/31/2024] [Accepted: 02/13/2025] [Indexed: 03/20/2025] Open
Abstract
Background Gastric cancer remains a prevalent malignancy worldwide, with peritoneal metastasis being the predominant form of recurrence and metastasis, which are clear predictors of prognosis. The aim of this comprehensive bibliometric analysis was to assess the current status of the research landscape and to identify impending trends in gastric cancer peritoneal metastasis (GCPM). Methods Relevant studies of GCPM were retrieved from the Web of Science Core Collection database. Qualified articles were screened based on the inclusion and exclusion criteria for further analysis. The selected publications were then subjected to bibliometric analysis utilizing VOSviewer software. Results In total, 1,100 publications were included for analysis. The results revealed a consistent upward trend in the number of publications annually from 2000 to 2024, with an anticipated continuation of this growth in future research. The National Cancer Center Japan, emerged as the institution with the most publications and Professor Kodera and Annals of Surgical Oncology were identified as the most influential author and journal, respectively, in the domain of GCPM. In terms of international collaborations, the USA, Japan, and France were the most engaged countries. Yonemura was recognized as the most frequently cited author. Gastrectomy, systemic chemotherapy, and intraperitoneal therapy are the current research hotspots within this domain. Conclusion Research related to GCPM had rapidly increased over the past two decades. These findings identify the most influential countries, institutions, authors, journals, and academic collaboration networks, while also clarifying hotspots and future trends in GCPM research.
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Affiliation(s)
- Manting Y
- College of Integrative Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Dongfang L
- Hunan Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
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Zheng Z, Zhai Y, Yan X, Wang Z, Zhang H, Xu R, Liu X, Cai J, Zhang Z, Shang Y, Zhang J, Yin J. Functions and Clinical Applications of Exosomes in Gastric Cancer. Int J Biol Sci 2025; 21:2330-2345. [PMID: 40083701 PMCID: PMC11900809 DOI: 10.7150/ijbs.98087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 02/04/2025] [Indexed: 03/16/2025] Open
Abstract
Gastric cancer is a common and highly invasive type of malignant tumor, the pathogenesis of which remains unclarified. However, exosomes are now known to play important roles in gastric cancer development and treatment. Cells use exosomes for the packaging and transportation of a variety of bioactive molecules, such as proteins, double-stranded DNA, and micro-ribonucleic acids, to other sites. Exosome-specific membrane structures and exosomal contents are widely involved in processes that facilitate material exchange and intercellular communication between gastric cancer cells. They help in forming a pre-metastatic microenvironment, promoting the proliferation and apoptosis of gastric cancer cells, and driving invasion, metastasis, and resistance to anti-tumor drugs. In this review, we aimed to summarize the findings of research articles indexed in the PubMed, Web of Science, and Embase databases and published up to May 31, 2024, on the role of exosomes in the pathogenesis of gastric cancer and their potential clinical applications in its treatment. Thus, research on exosomes may lead to breakthroughs in the early diagnosis of gastric cancer and identification of novel treatments.
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Affiliation(s)
- Zhi Zheng
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Institute of Clinical Medicine, Beijing, China
| | - Yuhao Zhai
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Institute of Clinical Medicine, Beijing, China
| | - Xiaosheng Yan
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Institute of Clinical Medicine, Beijing, China
| | - Zimeng Wang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Institute of Clinical Medicine, Beijing, China
| | - Haiqiao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Institute of Clinical Medicine, Beijing, China
| | - Rui Xu
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiaoye Liu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Institute of Clinical Medicine, Beijing, China
| | - Jun Cai
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Institute of Clinical Medicine, Beijing, China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Institute of Clinical Medicine, Beijing, China
| | - Yuxi Shang
- Department of Hematology, Fuxing Hospital, Eighth Clinical Medical College, Capital Medical University, Beijing, China
| | - Jun Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Institute of Clinical Medicine, Beijing, China
| | - Jie Yin
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
- National Clinical Research Center for Digestive Diseases, Beijing, China
- Beijing Institute of Clinical Medicine, Beijing, China
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Gao J, Yang R, Zhu X, Shi J, Wang S, Jing A. An Electrochemical Immunosensor for Sensitive Detection of Exosomes Based on Au/MXenes and AuPtPdCu. MICROMACHINES 2025; 16:280. [PMID: 40141891 PMCID: PMC11944654 DOI: 10.3390/mi16030280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/24/2025] [Accepted: 02/26/2025] [Indexed: 03/28/2025]
Abstract
Exosomes are important biomarkers for liquid biopsy in early cancer screening which play important roles in many biological processes, including apoptosis, inflammatory response, and tumor metastasis. In this study, an electrochemical aptamer immunosensor based on Au/MXene and AuPtPdCu was constructed for the sensitive detection of colorectal cancer-derived exosomes. AuNPs were deposited in situ on the surface of MXenes as a sensing platform due to their large specific area, excellent conductivity, and higher number of active sites for aptamer immobilization. The aptamer CD63 immobilized on Au/MXene can specifically capture target exosomes. Therefore, the AuPtPdCu-Apt nanoprobe further enhanced the sensitivity and accuracy of the immunosensor. A low limit of detection of 19 particles μL-1 was achieved in the linear range of 50 to 5 × 104 particles μL-1 under optimal conditions. The immunosensor developed herein showed satisfactory electrochemical stability and anti-interference ability for the detection of exosomes in real serum samples.
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Affiliation(s)
- Jie Gao
- School of Secondary Vocational Education, The Open University of China, Beijing 100031, China;
| | - Rong Yang
- School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang 471023, China; (R.Y.); (J.S.); (S.W.)
| | - Xiaorui Zhu
- Collaboration Innovative Center of Henan Province for Energy-Saving Building Materials, Xinyang Normal University, Xinyang 464000, China;
| | - Jiling Shi
- School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang 471023, China; (R.Y.); (J.S.); (S.W.)
| | - Sufei Wang
- School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang 471023, China; (R.Y.); (J.S.); (S.W.)
| | - Aihua Jing
- School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang 471023, China; (R.Y.); (J.S.); (S.W.)
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Moni ZA, Hasan Z, Alam MS, Roy N, Islam F. Diagnostic and Prognostic Significance of Exosomes and Their Components in Patients With Cancers. Cancer Med 2025; 14:e70569. [PMID: 39757782 DOI: 10.1002/cam4.70569] [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: 05/21/2024] [Revised: 12/15/2024] [Accepted: 12/21/2024] [Indexed: 01/07/2025] Open
Abstract
BACKGROUND Cancer is the second leading cause of human mortality worldwide. Extracellular vesicles (EVs) from liquid biopsy samples are used in early cancer detection, characterization, and surveillance. Exosomes are a subset of EVs produced by all cells and present in all body fluids. They play an important role in the development of cancer because they are active transporters capable of carrying the contents of any type of cell. The objective of this review was to provide a brief overview of the clinical implication of exosomes or exosomal components in cancer diagnosis and prognosis. METHODS An extensive review of the current literature of exosomes and their components in cancer diagnosis and prognosis were carried out in the current study. RESULTS Tumor cells release exosomes that contribute to the formation of the pre-metastatic microenvironment, angiogenesis, invasion, and treatment resistance. On the contrary, tumor cells release more exosomes than normal cells, and these tumor-specific exosomes can carry the genomic and proteomic signature contents of the tumor cells, which can act as tools for the diagnosis and prognosis of patients with cancers. CONCLUSION This information may help clinicians to improve the management of cancer patients in clinical settings in the future.
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Affiliation(s)
- Zinnat Ara Moni
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh
| | - Zahid Hasan
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh
| | - Md Shaheen Alam
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh
| | - Nitai Roy
- Department of Biochemistry and Molecular Biology, Patuakhali Science and Technology University, Patuakhali, Bangladesh
| | - Farhadul Islam
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh
- School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia
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Wang J, Zhang H, Li J, Ni X, Yan W, Chen Y, Shi T. Exosome-derived proteins in gastric cancer progression, drug resistance, and immune response. Cell Mol Biol Lett 2024; 29:157. [PMID: 39719600 PMCID: PMC11667977 DOI: 10.1186/s11658-024-00676-5] [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: 03/22/2024] [Accepted: 12/09/2024] [Indexed: 12/26/2024] Open
Abstract
Gastric cancer (GC) represents a prevalent malignancy globally, often diagnosed at advanced stages owing to subtle early symptoms, resulting in a poor prognosis. Exosomes are extracellular nano-sized vesicles and are secreted by various cells. Mounting evidence indicates that exosomes contain a wide range of molecules, such as DNA, RNA, lipids, and proteins, and play crucial roles in multiple cancers including GC. Recently, with the rapid development of mass spectrometry-based detection technology, researchers have paid increasing attention to exosomal cargo proteins. In this review, we discussed the origin of exosomes and the diagnostic and prognostic roles of exosomal proteins in GC. Moreover, we summarized the biological functions of exosomal proteins in GC processes, such as proliferation, metastasis, drug resistance, stemness, immune response, angiogenesis, and traditional Chinese medicine therapy. In summary, this review synthesizes current advancements in exosomal proteins associated with GC, offering insights that could pave the way for novel diagnostic and therapeutic strategies for GC in the foreseeable future.
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Affiliation(s)
- Jiayu Wang
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Road, Suzhou, 215000, China
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Huan Zhang
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Road, Suzhou, 215000, China
| | - Juntao Li
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiangyu Ni
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Road, Suzhou, 215000, China
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Wenying Yan
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, China.
- Center for Systems Biology, Soochow University, Suzhou, China.
- Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Suzhou, China.
| | - Yueqiu Chen
- Department of Cardiovascular Surgery of The First Affiliated Hospital and Institute for Cardiovascular Science, Suzhou Medical College of Soochow University, Soochow University, Suzhou, 215007, China.
| | - Tongguo Shi
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Road, Suzhou, 215000, China.
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
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Wu W, Yang J, Yu T, Zou Z, Huang X. The Role and Mechanism of TRIM Proteins in Gastric Cancer. Cells 2024; 13:2107. [PMID: 39768197 PMCID: PMC11674240 DOI: 10.3390/cells13242107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/13/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025] Open
Abstract
Tripartite motif (TRIM) family proteins, distinguished by their N-terminal region that includes a Really Interesting New Gene (RING) domain with E3 ligase activity, two B-box domains, and a coiled-coil region, have been recognized as significant contributors in carcinogenesis, primarily via the ubiquitin-proteasome system (UPS) for degrading proteins. Mechanistically, these proteins modulate a variety of signaling pathways, including Wnt/β-catenin, PI3K/AKT, and TGF-β/Smad, contributing to cellular regulation, and also impact cellular activities through non-signaling mechanisms, including modulation of gene transcription, protein degradation, and stability via protein-protein interactions. Currently, growing evidence indicates that TRIM proteins emerge as potential regulators in gastric cancer, exhibiting both tumor-suppressive and oncogenic roles. Given their critical involvement in cellular processes and the notable challenges of gastric cancer, exploring the specific contributions of TRIM proteins to this disease is necessary. Consequently, this review elucidates the roles and mechanisms of TRIM proteins in gastric cancer, emphasizing their potential as therapeutic targets and prognostic factors.
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Affiliation(s)
- Wangxi Wu
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China; (W.W.); (T.Y.)
- The Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang 330031, China; (J.Y.); (Z.Z.)
| | - Jinyu Yang
- The Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang 330031, China; (J.Y.); (Z.Z.)
| | - Tian Yu
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China; (W.W.); (T.Y.)
| | - Zhuoling Zou
- The Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang 330031, China; (J.Y.); (Z.Z.)
| | - Xuan Huang
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China; (W.W.); (T.Y.)
- Chongqing Research Institute, Nanchang University, Chongqing 400010, China
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Weng C, Jin R, Jin X, Yang Z, He C, Zhang Q, Xu J, Lv B. Exploring the Mechanisms, Biomarkers, and Therapeutic Targets of TRIM Family in Gastrointestinal Cancer. Drug Des Devel Ther 2024; 18:5615-5639. [PMID: 39654601 PMCID: PMC11626976 DOI: 10.2147/dddt.s482340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 11/23/2024] [Indexed: 12/12/2024] Open
Abstract
Gastrointestinal region (GI) cancers are closely linked to the ubiquitination system, with the E3 ubiquitin ligase playing a crucial role by targeting various substrates. As E3 ubiquitin ligases, proteins of tripartite motif (TRIM) family play a role in cancer signaling, development, apoptosis, and formation. These proteins regulate diverse biological activities and signaling pathways. This study comprehensively outlines the functions of TRIM proteins in gastrointestinal physiology, contributing to our knowledge of the molecular pathways involved in gastrointestinal tumors. Gastrointestinal region (GI) cancers are closely linked to the ubiquitination system, with the E3 ubiquitin ligase playing a crucial role by targeting various substrates.
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Affiliation(s)
- Chunyan Weng
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, People’s Republic of China
| | - Rijuan Jin
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, People’s Republic of China
| | - Xiaoliang Jin
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, People’s Republic of China
| | - Zimei Yang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, People’s Republic of China
| | - Chenghai He
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, People’s Republic of China
- Department of Gastroenterology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang Province, People’s Republic of China
| | - Qiuhua Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, People’s Republic of China
| | - Jingli Xu
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, People’s Republic of China
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, People’s Republic of China
| | - Bin Lv
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, People’s Republic of China
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Ma L, Guo H, Zhao Y, Liu Z, Wang C, Bu J, Sun T, Wei J. Liquid biopsy in cancer current: status, challenges and future prospects. Signal Transduct Target Ther 2024; 9:336. [PMID: 39617822 PMCID: PMC11609310 DOI: 10.1038/s41392-024-02021-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/10/2024] [Accepted: 10/14/2024] [Indexed: 12/06/2024] Open
Abstract
Cancer has a high mortality rate across the globe, and tissue biopsy remains the gold standard for tumor diagnosis due to its high level of laboratory standardization, good consistency of results, relatively stable samples, and high accuracy of results. However, there are still many limitations and drawbacks in the application of tissue biopsy in tumor. The emergence of liquid biopsy provides new ideas for early diagnosis and prognosis of tumor. Compared with tissue biopsy, liquid biopsy has many advantages in the diagnosis and treatment of various types of cancer, including non-invasive, quickly and so on. Currently, the application of liquid biopsy in tumor detection has received widely attention. It is now undergoing rapid progress, and it holds significant potential for future applications. Around now, liquid biopsies encompass several components such as circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. In addition, advances in the identification of liquid biopsy indicators have significantly enhanced the possibility of utilizing liquid biopsies in clinical settings. In this review, we will discuss the application, advantages and challenges of liquid biopsy in some common tumors from the perspective of diverse systems of tumors, and look forward to its future development prospects in the field of cancer diagnosis and treatment.
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Affiliation(s)
- Liwei Ma
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China.
| | - Huiling Guo
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Yunxiang Zhao
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhibo Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Chenran Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China
| | - Jiahao Bu
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Ting Sun
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- Key Clinical Laboratory of Henan province, Zhengzhou, Henan, China.
| | - Jianwei Wei
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
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Zhong Z, Ji J, Li H, Kang L, Zhu H. Proteomic analysis of plasma exosomes in patients with metastatic colorectal cancer. Clin Proteomics 2024; 21:58. [PMID: 39385083 PMCID: PMC11465920 DOI: 10.1186/s12014-024-09510-8] [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: 06/18/2024] [Accepted: 09/24/2024] [Indexed: 10/11/2024] Open
Abstract
BACKGROUND The diagnosis and treatment of colorectal cancer (CRC), especially metastatic colorectal cancer (mCRC), is a major priority and research challenge. We screened for expression differences in the plasma exosomal proteomes of patients with mCRC, those with CRC, and healthy controls (HCs) to discover potential biomarkers for mCRC. METHODS Plasma samples from five patients with mCRC, five patients with CRC, and five HCs were collected and processed to isolate exosomes by ultracentrifugation. Exosomal protein concentrations were determined using the BCA kit, and liquid chromatography-mass spectrometry was utilized to identify and analyze the proteins. RESULTS From the exosomes isolated from plasma samples, a total of 994 quantifiable proteins were detected, including 287 differentially expressed proteins identified by quantitative proteomics analyses. Totals of 965, 963 and 968 proteins were identified in mCRC patients, CRC patients, and HCs, respectively. The study identified 83 proteins with differential expression in the plasma exosomes of mCRC patients. The top 10 upregulated proteins in the mCRC group and CRC groups were ITGA4, GNAI1, SFTPA2, UGGT1, GRN, LBP, SMIM1, BMP1, HMGN5, and MFAP4, while the top 10 downregulated proteins were PSMB8, LCK, RAB35, PSMB4, CD81, CD63, GLIPR2, RAP1B, RAB30, and CES1. Western Blot validation data confirmed that ITGA4 and GNAI1 were unequivocally enriched in plasma-derived exosomes from mCRC patients. CONCLUSIONS These differential proteins offer potential new candidate molecules for further research on the pathogenesis of mCRC and the identification of therapeutic targets. This study sheds light on the potential significance of plasma exosome proteomics studies in our understanding and treatment of mCRC.
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Affiliation(s)
- Zhaoyue Zhong
- School of Public Health, Xinjiang Medical University, No. 567, Shangde North Road, Shuimogou District, Urumqi, 830017, Xinjiang, China
| | - Jiayin Ji
- School of Public Health, Xinjiang Medical University, No. 567, Shangde North Road, Shuimogou District, Urumqi, 830017, Xinjiang, China
| | - Hongxia Li
- School of Public Health, Xinjiang Medical University, No. 567, Shangde North Road, Shuimogou District, Urumqi, 830017, Xinjiang, China
| | - Ling Kang
- School of Public Health, Xinjiang Medical University, No. 567, Shangde North Road, Shuimogou District, Urumqi, 830017, Xinjiang, China.
| | - Haipeng Zhu
- Karamay Central Hospital, Number 67, Junggar Road, Karamay Region, Karamay, 834000, Xinjiang, China.
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Almutairy B, Alzahrani MS, Waggas DS, Alsaab HO. Particular exosomal micro-RNAs and gastrointestinal (GI) cancer cells' roles: Current theories. Exp Cell Res 2024; 442:114278. [PMID: 39383930 DOI: 10.1016/j.yexcr.2024.114278] [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: 08/26/2024] [Revised: 09/24/2024] [Accepted: 10/06/2024] [Indexed: 10/11/2024]
Abstract
A diverse range of gastrointestinal tract disorders are called gastrointestinal (GI) malignancies. The transformation of normal cells into precursor cells, precursor cells into premalignant cells, and premalignant cells into cancerous cells is facilitated by the interaction of many modifiable and non-modifiable risk factors. Developing relevant therapy alternatives based on a better knowledge of the illness's aetiology is essential to enhance patient outcomes. The exosome is crucial in regulating intercellular interaction because it may send molecular signals to nearby or distant cells. Exosomes produced from cancer can introduce a variety of chemicals and vast concentrations of microRNA (miRNA) into the tumour microenvironment. These miRNAs significantly impact immunological evasion, metastasis, apoptosis resistance, and cell growth. Exosomal miRNAs, or exosomal miRNAs, are essential for controlling cancer resistance to apoptosis, according to mounting data. Exosomal miRNAs function as an interaction hub between cancerous cells and the milieu around them, regulating gene expression and various signalling pathways. Our research examines the regulatory function of exosomal miRNAs in mediating interactions between cancer cells and the stromal and immunological cells that make up the surrounding milieu.
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Affiliation(s)
- Bandar Almutairy
- Department of Pharmacology, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia.
| | - Mohammad S Alzahrani
- Department of Clinical Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
| | - Dania S Waggas
- Pathological Sciences Department, Fakeeh College for Medical Sciences, Jeddah University, Saudi Arabia.
| | - Hashem O Alsaab
- Department of Pharmaceutics and Pharmaceutical Technology, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
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11
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Mirgh D, Sonar S, Ghosh S, Adhikari MD, Subramaniyan V, Gorai S, Anand K. Landscape of exosomes to modified exosomes: a state of the art in cancer therapy. RSC Adv 2024; 14:30807-30829. [PMID: 39328877 PMCID: PMC11426072 DOI: 10.1039/d4ra04512b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 09/03/2024] [Indexed: 09/28/2024] Open
Abstract
Exosomes are a subpopulation of extracellular vesicles (EVs) that naturally originate from endosomes. They play a significant role in cellular communication. Tumor-secreted exosomes play a crucial role in cancer development and significantly contribute to tumorigenesis, angiogenesis, and metastasis by intracellular communication. Tumor-derived exosomes (TEXs) are a promising biomarker source of cancer detection in the early stages. On the other hand, they offer revolutionary cutting-edge approaches to cancer therapeutics. Exosomes offer a cell-free approach to cancer therapeutics, which overcomes immune cell and stem cell therapeutics-based limitations (complication, toxicity, and cost of treatment). There are multiple sources of therapeutic exosomes present (stem cells, immune cells, plant cells, and synthetic and modified exosomes). This article explores the dynamic source of exosomes (plants, mesenchymal stem cells, and immune cells) and their modification (chimeric, hybrid exosomes, exosome-based CRISPR, and drug delivery) based on cancer therapeutic development. This review also highlights exosomes based clinical trials and the challenges and future orientation of exosome research. We hope that this article will inspire researchers to further explore exosome-based cancer therapeutic platforms for precision oncology.
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Affiliation(s)
- Divya Mirgh
- Vaccine and Immunotherapy Centre, Massachusetts General Hospital Boston USA
| | - Swarup Sonar
- Center for Global Health Research, Saveetha Medical College & Hospitals, Saveetha Institute of Medical and Technical Sciences Chennai Tamil Nadu 602105 India
| | - Srestha Ghosh
- Department of Microbiology, Lady Brabourne College Kolkata West Bengal 700017 India
| | - Manab Deb Adhikari
- Department of Biotechnology, University of North Bengal Darjeeling West Bengal India
| | - Vetriselvan Subramaniyan
- Department of Medical Sciences, School of Medical and Life Sciences, Sunway University Bandar Sunway Subang Jaya Selangor 47500 Malaysia
| | - Sukhamoy Gorai
- Department of Neurological Sciences, Rush University Medical Center Chicago IL USA
| | - Krishnan Anand
- Precision Medicine and Integrated Nano-Diagnostics (P-MIND) Research Group, Faculty of Health Sciences, University of the Free State Bloemfontein 9300 South Africa
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12
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Wang Y, Liang C, Liu X, Cheng SQ. A novel tumor-derived exosomal gene signature predicts prognosis in patients with pancreatic cancer. Transl Cancer Res 2024; 13:4324-4340. [PMID: 39262474 PMCID: PMC11384923 DOI: 10.21037/tcr-23-2354] [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: 12/23/2023] [Accepted: 06/02/2024] [Indexed: 09/13/2024]
Abstract
Background Pancreatic cancer is a devastating disease with poor prognosis. Accumulating evidence has shown that exosomes and their cargo have the potential to mediate the progression of pancreatic cancer and are promising non-invasive biomarkers for the early detection and prognosis of this malignancy. This study aimed to construct a gene signature from tumor-derived exosomes with high prognostic capacity for pancreatic cancer using bioinformatics analysis. Methods Gene expression data of solid pancreatic cancer tumors and blood-derived exosome tissues were downloaded from The Cancer Genome Atlas (TCGA) and ExoRBase 2.0. Overlapping differentially expressed genes (DEGs) in the two datasets were analyzed, followed by functional enrichment analysis, protein-protein interaction networks, and weighted gene co-expression network analysis (WGCNA). Using the least absolute shrinkage and selection operator (LASSO) regression of prognosis-related exosomal DEGs, a tumor-derived exosomal gene signature was constructed based on the TCGA dataset, which was validated by an external validation dataset, GSE62452. The prognostic power of this gene signature and its relationship with various pathways and immune cell infiltration were analyzed. Results A total of 166 overlapping DEGs were identified from the two datasets, which were markedly enriched in functions and pathways associated with the cell cycle. Two key modules and corresponding 70 exosomal DEGs were identified using WGCNA. Using LASSO Cox regression of prognosis-related exosomal DEGs, a tumor-derived exosomal gene signature was built using six exosomal DEGs (ARNTL2, FHL2, KRT19, MMP1, CDCA5, and KIF11), which showed high predictive performance for prognosis in both the training and validation datasets. In addition, this prognostic signature is associated with the differential activation of several pathways, such as the cell cycle, and the infiltration of some immune cells, such as Tregs and CD8+ T cells. Conclusions This study established a six-exosome gene signature that can accurately predict the prognosis of pancreatic cancer.
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Affiliation(s)
- Yang Wang
- Department of Hepatopancreatobiliary Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Chao Liang
- Department of Hepatopancreatobiliary Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xinbo Liu
- Department of Hepatopancreatobiliary Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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13
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Sun AH, Zhang XY, Huang YY, Chen L, Wang Q, Jiang XC. Prognostic value and predictive model of tumor markers in stage I to III gastric cancer patients. World J Clin Oncol 2024; 15:1033-1047. [PMID: 39193154 PMCID: PMC11346068 DOI: 10.5306/wjco.v15.i8.1033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 07/03/2024] [Accepted: 07/24/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Preoperative serum tumor markers have been widely used in the diagnosis and treatment of gastric cancer patients. However, few studies have evaluated the prognosis of gastric cancer patients by establishing statistical models with multiple serum tumor indicators. AIM To explore the prognostic value and predictive model of tumor markers in stage I and III gastric cancer patients. METHODS From October 2018 to April 2020, a total of 1236 patients with stage I to III gastric cancer after surgery were included in our study. The relationship between serum tumor markers and clinical and pathological data were analyzed. We established a statistical model to predict the prognosis of gastric cancer based on the results of COX regression analysis. Overall survival (OS) was also compared across different stages of gastric cancer. RESULTS The deadline for follow-up was May 31, 2023. A total of 1236 patients were included in our study. Univariate analysis found that age, clinical stage, T and N stage, tumor location, differentiation, Borrmann type, size, and four serum tumor markers were prognostic factors of OS (P < 0.05). It was shown that clinical stage, tumor size, alpha foetoprotein, carcinoembryonic antigen, CA125 and CA19-9 (P < 0.05) were independent prognostic factors for OS. According to the scoring results obtained from the statistical model, we found that patients with high scores had poorer survival time (P < 0.05). Furthermore, in stage I patients, the 3-year OS for scores 0-3 ranged from 96.85%, 95%, 85%, and 80%. In stage II patients, the 3-year OS for scores 0-4 were 88.6%, 76.5%, 90.5%, 65.5% and 60%. For stage III patients, 3-year OS for scores 0-6 were 70.9%, 68.3%, 64.1%, 50.9%, 38.4%, 18.5% and 5.2%. We also analyzed the mean survival of patients with different scores. For stage I patients, the mean OS was 55.980 months. In stage II, the mean OS was 51.550 months. The mean OS for stage III was 39.422 months. CONCLUSION Our statistical model can effectively predict the prognosis of gastric cancer patients.
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Affiliation(s)
- Ai-Hua Sun
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
| | - Xin-Yu Zhang
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
| | - Yang-Yang Huang
- Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou 350001, China
| | - Lei Chen
- Department of General Surgery, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China
| | - Qing Wang
- Department of General Surgery, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China
| | - Xiao-Cong Jiang
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
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14
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Liao H, Zhang C, Wang F, Jin F, Zhao Q, Wang X, Wang S, Gao J. Tumor-derived extracellular vesicle proteins as new biomarkers and targets in precision oncology. J Mol Med (Berl) 2024; 102:961-971. [PMID: 38814362 PMCID: PMC11269371 DOI: 10.1007/s00109-024-02452-6] [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: 11/15/2023] [Revised: 04/09/2024] [Accepted: 04/25/2024] [Indexed: 05/31/2024]
Abstract
Extracellular vesicles (EVs) are important carriers of signaling molecules, such as nucleic acids, proteins, and lipids, and have become a focus of increasing interest due to their numerous physiological and pathological functions. For a long time, most studies on EV components focused on noncoding RNAs; however, in recent years, extracellular vesicle proteins (EVPs) have been found to play important roles in diagnosis, treatment, and drug resistance and thus have been considered favorable biomarkers and therapeutic targets for various tumors. In this review, we describe the general protocols of research on EVPs and summarize their multifaceted roles in precision medicine applications, including cancer diagnosis, dynamic monitoring of therapeutic efficacy, drug resistance research, tumor microenvironment interaction research, and anticancer drug delivery.
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Affiliation(s)
- Haiyan Liao
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, China
| | - Cheng Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Fen Wang
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, China
| | - Feng Jin
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, China
| | - Qiqi Zhao
- Chi Biotech Co., Ltd., Shenzhen, China
| | | | - Shubin Wang
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
| | - Jing Gao
- Department of Oncology, Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
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15
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Deng NH, Tian Z, Zou YJ, Quan SB. E3 ubiquitin ligase TRIM31: A potential therapeutic target. Biomed Pharmacother 2024; 176:116846. [PMID: 38850648 DOI: 10.1016/j.biopha.2024.116846] [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: 03/13/2024] [Revised: 05/13/2024] [Accepted: 05/27/2024] [Indexed: 06/10/2024] Open
Abstract
Ubiquitination is a key mechanism for post-translational protein modification, affecting protein localization, metabolism, degradation and various cellular physiological processes. Dysregulation of ubiquitination is associated with the pathogenesis of various diseases, such as tumors and cardiovascular diseases, making it a primary area of interest in biochemical research and drug development endeavors. E3 ubiquitin ligases play a pivotal role in modulating the ubiquitination of substrate proteins through their unique recognition functions. TRIM31, a member of the TRIM family of E3 ubiquitin ligases, is aberrantly expressed in different pathophysiological conditions. The biological function of TRIM31 is associated with the occurrence and development of diverse diseases. TRIM31 has been demonstrated to inhibit inflammation by promoting ubiquitin-proteasome-mediated degradation of the sensing protein NLRP3 in the inflammasome. TRIM31 mediates ubiquitination of MAVS, inducing the formation of prion-like aggregates, and triggering innate antiviral immune responses. TRIM31 is also implicated in tumor pathophysiology through its ability to promote ubiquitination of the tumor suppressor protein p53. These findings indicate that TRIM31 is a potential therapeutic target, and subsequent in-depth research of TRIM31 is anticipated to provide information on its clinical application in therapy.
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Affiliation(s)
- Nian-Hua Deng
- The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, Guangdong 523326, PR China
| | - Zhen Tian
- The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, Guangdong 523326, PR China
| | - Ying-Jiao Zou
- Medical Technology Center, Shilong Town Community Health Service Center, Dongguan, Guangdong 523326, PR China
| | - Shou-Bo Quan
- The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, Guangdong 523326, PR China.
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16
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Lavi Arab F, Hoseinzadeh A, Hafezi F, Sadat Mohammadi F, Zeynali F, Hadad Tehran M, Rostami A. Mesenchymal stem cell-derived exosomes for management of prostate cancer: An updated view. Int Immunopharmacol 2024; 134:112171. [PMID: 38701539 DOI: 10.1016/j.intimp.2024.112171] [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: 02/25/2024] [Revised: 04/16/2024] [Accepted: 04/27/2024] [Indexed: 05/05/2024]
Abstract
Prostate cancer represents the second most prevalent form of cancer found in males, and stands as the fifth primary contributor to cancer-induced mortality on a global scale. Research has shown that transplanted mesenchymal stem cells (MSCs) can migrate by homing to tumor sites in the body. In prostate cancer, researchers have explored the fact that MSC-based therapies (including genetically modified delivery vehicles or vectors) and MSC-derived exosomes are emerging as attractive options to improve the efficacy and safety of traditional cancer therapies. In addition, researchers have reported new insights into the application of extracellular vesicle (EV)-MSC therapy as a novel treatment option that could provide a more effective and targeted approach to prostate cancer treatment. Moreover, the new generation of exosomes, which contain biologically functional molecules as signal transducers between cells, can simultaneously deliver different therapeutic agents and induce an anti-tumor phenotype in immune cells and their recruitment to the tumor site. The results of the current research on the use of MSCs in the treatment of prostate cancer may be helpful to researchers and clinicians working in this field. Nevertheless, it is crucial to emphasize that although dual-role MSCs show promise as a therapeutic modality for managing prostate cancer, further investigation is imperative to comprehensively grasp their safety and effectiveness. Ongoing clinical trials are being conducted to assess the viability of MSCs in the management of prostate cancer. The results of these trials will help determine the viability of this approach. Based on the current literature, engineered MSCs-EV offer great potential for application in targeted tumor therapy.
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Affiliation(s)
- Fahimeh Lavi Arab
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Akram Hoseinzadeh
- Department of Immunology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.; Cancer Research Center, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Fatemeh Hafezi
- Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Sadat Mohammadi
- Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Farid Zeynali
- Department of Urology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Melika Hadad Tehran
- Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
| | - Amirreza Rostami
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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17
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Díaz del Arco C, Fernández Aceñero MJ, Ortega Medina L. Liquid biopsy for gastric cancer: Techniques, applications, and future directions. World J Gastroenterol 2024; 30:1680-1705. [PMID: 38617733 PMCID: PMC11008373 DOI: 10.3748/wjg.v30.i12.1680] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 02/01/2024] [Accepted: 03/08/2024] [Indexed: 03/28/2024] Open
Abstract
After the study of circulating tumor cells in blood through liquid biopsy (LB), this technique has evolved to encompass the analysis of multiple materials originating from the tumor, such as nucleic acids, extracellular vesicles, tumor-educated platelets, and other metabolites. Additionally, research has extended to include the examination of samples other than blood or plasma, such as saliva, gastric juice, urine, or stool. LB techniques are diverse, intricate, and variable. They must be highly sensitive, and pre-analytical, patient, and tumor-related factors significantly influence the detection threshold, diagnostic method selection, and potential results. Consequently, the implementation of LB in clinical practice still faces several challenges. The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases, monitoring treatment response, early identification of relapses, or assessing patient risk. On the other hand, gastric cancer (GC) is a disease often diagnosed at advanced stages. Despite recent advances in molecular understanding, the currently available treatment options have not substantially improved the prognosis for many of these patients. The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients. In this comprehensive review, from a pathologist's perspective, we provide an overview of the main options available in LB, delve into the fundamental principles of the most studied techniques, explore the potential utility of LB application in the context of GC, and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.
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Affiliation(s)
- Cristina Díaz del Arco
- Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, Madrid 28040, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28040, Spain
| | - M Jesús Fernández Aceñero
- Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, Madrid 28040, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28040, Spain
| | - Luis Ortega Medina
- Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, Madrid 28040, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28040, Spain
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18
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Guan XL, Guan XY, Zhang ZY. Roles and application of exosomes in the development, diagnosis and treatment of gastric cancer. World J Gastrointest Oncol 2024; 16:630-642. [PMID: 38577463 PMCID: PMC10989387 DOI: 10.4251/wjgo.v16.i3.630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 12/18/2023] [Accepted: 01/15/2024] [Indexed: 03/12/2024] Open
Abstract
As important messengers of intercellular communication, exosomes can regulate local and distant cellular communication by transporting specific exosomal contents and can also promote or suppress the development and progression of gastric cancer (GC) by regulating the growth and proliferation of tumor cells, the tumor-related immune response and tumor angiogenesis. Exosomes transport bioactive molecules including DNA, proteins, and RNA (coding and noncoding) from donor cells to recipient cells, causing reprogramming of the target cells. In this review, we will describe how exosomes regulate the cellular immune response, tumor angiogenesis, proliferation and metastasis of GC cells, and the role and mechanism of exosome-based therapy in human cancer. We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treatment of GC and their relationship with drug resistance.
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Affiliation(s)
- Xiao-Li Guan
- Department of General Medicine, The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Xiao-Ying Guan
- Department of Pathology, The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
| | - Zheng-Yi Zhang
- Department of General Medicine, The Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
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19
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Wang M, Shu H, Cheng X, Xiao H, Jin Z, Yao N, Mao S, Zong Z. Exosome as a crucial communicator between tumor microenvironment and gastric cancer (Review). Int J Oncol 2024; 64:28. [PMID: 38240092 PMCID: PMC10836496 DOI: 10.3892/ijo.2024.5616] [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: 10/18/2023] [Accepted: 01/03/2024] [Indexed: 01/23/2024] Open
Abstract
Gastric cancer is one of the most common malignancies and has relatively high morbidity and mortality rates. Exosomes are nanoscale extracellular vesicles that originate from a diverse array of cells and may be found throughout various bodily fluids. These vesicles are endogenous nanocarriers in their natural state with the unique ability to transport lipids, proteins, DNA and RNA. Exosomes contain DNA, RNA, proteins, lipids and other bioactive components that have crucial roles in the transmission of information and regulation of cell activities in gastric cancer. This paper begins with an exploration of the composition, formation and release mechanisms of exosomes. Subsequently, the role of exosomes in the tumor microenvironment is reviewed in terms of the immune cell population, nonimmune cell population and other factors. Finally, the current status and challenges of exosome‑based research on the progression, diagnosis and therapeutic methods of gastric cancer are summarized. This holistic review offers insight that may guide future research directions for exosomes and potentially pave the way for novel therapeutic interventions in the management of gastric cancer.
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Affiliation(s)
- Menghui Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
- HuanKui Academy, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Hongxin Shu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Xifu Cheng
- School of Ophthalmology and Optometry, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Hong Xiao
- Queen Marry College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Zhenhua Jin
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Nan Yao
- Queen Marry College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Shengxun Mao
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Zhen Zong
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
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20
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Zuo Q, Xu Q, Li Z, Luo D, Peng H, Duan Z. TRIM3 inhibits colorectal cancer cell migration and lipid droplet formation by promoting FABP4 degradation. Histol Histopathol 2024; 39:239-250. [PMID: 37212515 DOI: 10.14670/hh-18-627] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
This study is to investigate the regulation of TRIM3/FABP4 on colorectal cancer (CRC) cell migration and lipid metabolism. After transfection of HCT116, LoVo, or SW480 cells, the expression of FABP4, TRIM3, N-cadherin, Vimentin, E-cadherin, and lipid droplet (LD) formation-related genes was measured by qRT-PCR or western blot assays. Wound healing and Transwell assays were applied to detect CRC cell migration and invasion abilities. The levels of triglyceride (TG) and total cholesterol (TC) were measured and the formation of LDs was observed. Additionally, the relationship between FABP4 and TRIM3 was confirmed by Co-IP and ubiquitination assays. Furthermore, a liver metastasis model of CRC was established to explore the effect of FABP4 on CRC tumor metastasis in vivo. FABP4 was upregulated in CRC cells. Downregulation of FABP4 or upregulation of TRIM3 resulted in repressed cell migration and invasion, decreased TG and TC levels, and reduced numbers of LDs. In nude mice, knockdown of FABP4 reduced metastatic nodules in the liver. Mechanistically, TRIM3 combined FABP4 and decreased its protein expression by ubiquitination. Overexpressed FABP4 reversed the influence of TRIM3 upregulation on CRC cell migration and LD formation. In conclusion, underexpressed TRIM3 suppressed FABP4 ubiquitination and accelerated CRC cell migration and LD formation.
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Affiliation(s)
- Qi Zuo
- Department of Emergency, The First Hospital of Changsha, Changsha, Hunan, PR China
| | - Qimei Xu
- Department of Pathology, The First Hospital of Changsha, Changsha, Hunan, PR China
| | - Zhen Li
- Department of Pathology, The First Hospital of Changsha, Changsha, Hunan, PR China
| | - Dixian Luo
- Department of Laboratory Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong, PR China
| | - Hanwu Peng
- Department of Emergency, The First Hospital of Changsha, Changsha, Hunan, PR China
| | - Zhi Duan
- Department of Pathology, The First Hospital of Changsha, Changsha, Hunan, PR China.
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Schneider N, Hermann PC, Eiseler T, Seufferlein T. Emerging Roles of Small Extracellular Vesicles in Gastrointestinal Cancer Research and Therapy. Cancers (Basel) 2024; 16:567. [PMID: 38339318 PMCID: PMC10854789 DOI: 10.3390/cancers16030567] [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: 12/13/2023] [Revised: 01/22/2024] [Accepted: 01/25/2024] [Indexed: 02/12/2024] Open
Abstract
Discovered in the late eighties, sEVs are small extracellular nanovesicles (30-150 nm diameter) that gained increasing attention due to their profound roles in cancer, immunology, and therapeutic approaches. They were initially described as cellular waste bins; however, in recent years, sEVs have become known as important mediators of intercellular communication. They are secreted from cells in substantial amounts and exert their influence on recipient cells by signaling through cell surface receptors or transferring cargos, such as proteins, RNAs, miRNAs, or lipids. A key role of sEVs in cancer is immune modulation, as well as pro-invasive signaling and formation of pre-metastatic niches. sEVs are ideal biomarker platforms, and can be engineered as drug carriers or anti-cancer vaccines. Thus, sEVs further provide novel avenues for cancer diagnosis and treatment. This review will focus on the role of sEVs in GI-oncology and delineate their functions in cancer progression, diagnosis, and therapeutic use.
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Affiliation(s)
- Nora Schneider
- Department for Internal Medicine 1, University Clinic Ulm, 89081 Ulm, Germany; (P.C.H.); (T.S.)
| | | | - Tim Eiseler
- Correspondence: (N.S.); (T.E.); Tel.: +49-731-500-44678 (N.S.); +49-731-500-44523 (T.E.)
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22
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Lei Y, Cai S, Zhang CD, Li YS. The biological role of extracellular vesicles in gastric cancer metastasis. Front Cell Dev Biol 2024; 12:1323348. [PMID: 38333593 PMCID: PMC10850573 DOI: 10.3389/fcell.2024.1323348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 01/15/2024] [Indexed: 02/10/2024] Open
Abstract
Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, and lipids. EVs play a crucial biological role in the process of GC metastasis. Through mechanisms such as remodeling the tumor microenvironment (TME), immune suppression, promoting angiogenesis, and facilitating epithelial-mesenchymal transition (EMT) and mesothelial-mesenchymal transition (MMT), EVs promote invasion and metastasis in GC. Further exploration of the biological roles of EVs will contribute to our understanding of the mechanisms underlying GC metastasis and may provide novel targets and strategies for the diagnosis and treatment of GC. In this review, we summarize the mechanisms by which EVs influence GC metastasis from four aspects: remodeling the TME, modulating the immune system, influencing angiogenesis, and modulating the processes of EMT and MMT. Finally, we briefly summarized the organotropism of GC metastasis as well as the potential and limitations of EVs in GC.
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Affiliation(s)
- Yun Lei
- Department of Surgical Oncology and 8th General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Shuang Cai
- Department of Gastroenterology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Chun-Dong Zhang
- Department of Surgical Oncology and 8th General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yong-Shuang Li
- Department of Surgical Oncology and 8th General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
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23
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Gu J, Chen J, Xiang S, Zhou X, Li J. Intricate confrontation: Research progress and application potential of TRIM family proteins in tumor immune escape. J Adv Res 2023; 54:147-179. [PMID: 36736694 DOI: 10.1016/j.jare.2023.01.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 01/06/2023] [Accepted: 01/12/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Tripartite motif (TRIM) family proteins have more than 80 members and are widely found in various eukaryotic cells. Most TRIM family proteins participate in the ubiquitin-proteasome degradation system as E3-ubiquitin ligases; therefore, they play pivotal regulatory roles in the occurrence and development of tumors, including tumor immune escape. Due to the diversity of functional domains of TRIM family proteins, they can extensively participate in multiple signaling pathways of tumor immune escape through different substrates. In current research and clinical contexts, immune escape has become an urgent problem. The extensive participation of TRIM family proteins in curing tumors or preventing postoperative recurrence and metastasis makes them promising targets. AIM OF REVIEW The aim of the review is to make up for the gap in the current research on TRIM family proteins and tumor immune escape and propose future development directions according to the current progress and problems. KEY SCIENTIFIC CONCEPTS OF REVIEW This up-to-date review summarizes the characteristics and biological functions of TRIM family proteins, discusses the mechanisms of TRIM family proteins involved in tumor immune escape, and highlights the specific mechanism from the level of structure-function-molecule-pathway-phenotype, including mechanisms at the level of protein domains and functions, at the level of molecules and signaling pathways, and at the level of cells and microenvironments. We also discuss the application potential of TRIM family proteins in tumor immunotherapy, such as possible treatment strategies for combination targeting TRIM family protein drugs and checkpoint inhibitors for improving cancer treatment.
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Affiliation(s)
- Junjie Gu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jingyi Chen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Shuaixi Xiang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China
| | - Xikun Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
| | - Jing Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
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Repetto O, Vettori R, Steffan A, Cannizzaro R, De Re V. Circulating Proteins as Diagnostic Markers in Gastric Cancer. Int J Mol Sci 2023; 24:16931. [PMID: 38069253 PMCID: PMC10706891 DOI: 10.3390/ijms242316931] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/22/2023] [Accepted: 11/24/2023] [Indexed: 12/18/2023] Open
Abstract
Gastric cancer (GC) is a highly malignant disease affecting humans worldwide and has a poor prognosis. Most GC cases are detected at advanced stages due to the cancer lacking early detectable symptoms. Therefore, there is great interest in improving early diagnosis by implementing targeted prevention strategies. Markers are necessary for early detection and to guide clinicians to the best personalized treatment. The current semi-invasive endoscopic methods to detect GC are invasive, costly, and time-consuming. Recent advances in proteomics technologies have enabled the screening of many samples and the detection of novel biomarkers and disease-related signature signaling networks. These biomarkers include circulating proteins from different fluids (e.g., plasma, serum, urine, and saliva) and extracellular vesicles. We review relevant published studies on circulating protein biomarkers in GC and detail their application as potential biomarkers for GC diagnosis. Identifying highly sensitive and highly specific diagnostic markers for GC may improve patient survival rates and contribute to advancing precision/personalized medicine.
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Affiliation(s)
- Ombretta Repetto
- Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Roberto Vettori
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy; (R.V.); (A.S.)
| | - Agostino Steffan
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy; (R.V.); (A.S.)
| | - Renato Cannizzaro
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy;
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy
| | - Valli De Re
- Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy
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25
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Wang C, Li W, Shao L, Zhou A, Zhao M, Li P, Zhang Z, Wu J. Both extracellular vesicles from helicobacter pylori-infected cells and helicobacter pylori outer membrane vesicles are involved in gastric/extragastric diseases. Eur J Med Res 2023; 28:484. [PMID: 37932800 PMCID: PMC10626716 DOI: 10.1186/s40001-023-01458-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 10/18/2023] [Indexed: 11/08/2023] Open
Abstract
Bacterial-derived extracellular vesicles (EVs) have emerged as crucial mediators in the cross-talk between hosts and pathogens, playing a significant role in infectious diseases and cancers. Among these pathogens, Helicobacter pylori (H. pylori) is a particularly important bacterium implicated in various gastrointestinal disorders, gastric cancers, and systemic illnesses. H. pylori achieves these effects by stimulating host cells to secrete EVs and generating internal outer membrane vesicles (OMVs). The EVs derived from H. pylori-infected host cells modulate inflammatory signaling pathways, thereby affecting cell proliferation, apoptosis, cytokine release, immune cell modification, and endothelial dysfunction, as well as disrupting cellular junctional structures and inducing cytoskeletal reorganization. In addition, OMVs isolated from H. pylori play a pivotal role in shaping subsequent immunopathological responses. These vesicles incite both inflammatory and immunosuppressive reactions within the host environment, facilitating pathogen evasion of host defenses and invasion of host cells. Despite this growing understanding, research involving H. pylori-derived EVs remains in its early stages across different domains. In this comprehensive review, we present recent advancements elucidating the contributions of EV components, such as non-coding RNAs (ncRNAs) and proteins, to the pathogenesis of gastric and extragastric diseases. Furthermore, we highlight their potential utility as biomarkers, therapeutic targets, and vehicles for targeted delivery.
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Affiliation(s)
- Chengyao Wang
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Wenkun Li
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Linlin Shao
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Anni Zhou
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Mengran Zhao
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Peng Li
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Zheng Zhang
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
| | - Jing Wu
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
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26
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Guo X, Peng Y, Song Q, Wei J, Wang X, Ru Y, Xu S, Cheng X, Li X, Wu D, Chen L, Wei B, Lv X, Ji G. A Liquid Biopsy Signature for the Early Detection of Gastric Cancer in Patients. Gastroenterology 2023; 165:402-413.e13. [PMID: 36894035 DOI: 10.1053/j.gastro.2023.02.044] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 02/02/2023] [Accepted: 02/20/2023] [Indexed: 03/11/2023]
Abstract
BACKGROUND & AIMS Diagnosing gastric cancer (GC) while the disease remains eligible for surgical resection is challenging. In view of this clinical challenge, novel and robust biomarkers for early detection thus improving prognosis of GC are necessary. The present study is to develop a blood-based long noncoding RNA (LR) signature for the early-detection of GC. METHODS The present 3-step study incorporated data from 2141 patients, including 888 with GC, 158 with chronic atrophic gastritis, 193 with intestinal metaplasia, 501 healthy donors, and 401 with other gastrointestinal cancers. The LR profile of stage I GC tissue samples were analyzed using transcriptomic profiling in discovery phase. The extracellular vesicle (EV)-derived LR signature was identified with a training cohort (n = 554) and validated with 2 external cohorts (n = 429 and n = 504) and a supplemental cohort (n = 69). RESULTS In discovery phase, one LR (GClnc1) was found to be up-regulated in both tissue and circulating EV samples with an area under the curve (AUC) of 0.9369 (95% confidence interval [CI], 0.9073-0.9664) for early-stage GC (stage I/II). The diagnostic performance of this biomarker was further confirmed in 2 external validation cohorts (Xi'an cohort, AUC: 0.8839; 95% CI: 0.8336-0.9342; Beijing cohort, AUC: 0.9018; 95% CI: 0.8597-0.9439). Moreover, EV-derived GClnc1 robustly distinguished early-stage GC from precancerous lesions (chronic atrophic gastritis and intestinal metaplasia) and GC with negative traditional gastrointestinal biomarkers (CEA, CA72-4, and CA19-9). The low levels of this biomarker in postsurgery and other gastrointestinal tumor plasma samples indicated its GC specificity. CONCLUSIONS EV-derived GClnc1 serves as a circulating biomarker for the early detection of GC, thus providing opportunities for curative surgery and improved survival outcomes.
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Affiliation(s)
- Xin Guo
- Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Department of Endoscopic Surgery, Air Force 986(th) Hospital, Fourth Military Medical University, Xi'an, China; Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yunhua Peng
- Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China
| | - Qiying Song
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Jiangpeng Wei
- Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xinxin Wang
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yi Ru
- Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China
| | - Shenhui Xu
- Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xin Cheng
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xiaohua Li
- Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Di Wu
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Lubin Chen
- Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Department of Endoscopic Surgery, Air Force 986(th) Hospital, Fourth Military Medical University, Xi'an, China
| | - Bo Wei
- Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Xiaohui Lv
- Department of Gynecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
| | - Gang Ji
- Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
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27
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Fan S, Poetsch A. Proteomic Research of Extracellular Vesicles in Clinical Biofluid. Proteomes 2023; 11:proteomes11020018. [PMID: 37218923 DOI: 10.3390/proteomes11020018] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 04/14/2023] [Accepted: 04/28/2023] [Indexed: 05/24/2023] Open
Abstract
Extracellular vesicles (EVs), the lipid bilayer membranous structures of particles, are produced and released from almost all cells, including eukaryotes and prokaryotes. The versatility of EVs has been investigated in various pathologies, including development, coagulation, inflammation, immune response modulation, and cell-cell communication. Proteomics technologies have revolutionized EV studies by enabling high-throughput analysis of their biomolecules to deliver comprehensive identification and quantification with rich structural information (PTMs, proteoforms). Extensive research has highlighted variations in EV cargo depending on vesicle size, origin, disease, and other features. This fact has sparked activities to use EVs for diagnosis and treatment to ultimately achieve clinical translation with recent endeavors summarized and critically reviewed in this publication. Notably, successful application and translation require a constant improvement of methods for sample preparation and analysis and their standardization, both of which are areas of active research. This review summarizes the characteristics, isolation, and identification approaches for EVs and the recent advances in EVs for clinical biofluid analysis to gain novel knowledge by employing proteomics. In addition, the current and predicted future challenges and technical barriers are also reviewed and discussed.
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Affiliation(s)
- Shipan Fan
- School of Basic Medical Sciences, Nanchang University, Nanchang 330021, China
| | - Ansgar Poetsch
- Queen Mary School, Medical College, Nanchang University, Nanchang 330021, China
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28
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David P, Mittelstädt A, Kouhestani D, Anthuber A, Kahlert C, Sohn K, Weber GF. Current Applications of Liquid Biopsy in Gastrointestinal Cancer Disease-From Early Cancer Detection to Individualized Cancer Treatment. Cancers (Basel) 2023; 15:cancers15071924. [PMID: 37046585 PMCID: PMC10093361 DOI: 10.3390/cancers15071924] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/20/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Worldwide, gastrointestinal (GI) cancers account for a significant amount of cancer-related mortality. Tests that allow an early diagnosis could lead to an improvement in patient survival. Liquid biopsies (LBs) due to their non-invasive nature as well as low risk are the current focus of cancer research and could be a promising tool for early cancer detection. LB involves the sampling of any biological fluid (e.g., blood, urine, saliva) to enrich and analyze the tumor's biological material. LBs can detect tumor-associated components such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and circulating tumor cells (CTCs). These components can reflect the status of the disease and can facilitate clinical decisions. LBs offer a unique and new way to assess cancers at all stages of treatment, from cancer screenings to prognosis to management of multidisciplinary therapies. In this review, we will provide insights into the current status of the various types of LBs enabling early detection and monitoring of GI cancers and their use in in vitro diagnostics.
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Affiliation(s)
- Paul David
- Department of Surgery, University Hospital of Erlangen, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Anke Mittelstädt
- Department of Surgery, University Hospital of Erlangen, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Dina Kouhestani
- Department of Surgery, University Hospital of Erlangen, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Anna Anthuber
- Department of Surgery, University Hospital of Erlangen, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Christoph Kahlert
- Department of Surgery, Carl Gustav Carus University Hospital, 01307 Dresden, Germany
| | - Kai Sohn
- Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany
| | - Georg F Weber
- Department of Surgery, University Hospital of Erlangen, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, 91054 Erlangen, Germany
- Deutsches Zentrum für Immuntherapie, University Hospital of Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
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29
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Zhou W, Ma J, Zhao H, Wang Q, Guo X, Chen L, Cao Z, Xu J, Zhang B, Zhou X. Serum exosomes from epithelial ovarian cancer patients contain LRP1, which promotes the migration of epithelial ovarian cancer cell. Mol Cell Proteomics 2023; 22:100520. [PMID: 36842607 PMCID: PMC10113894 DOI: 10.1016/j.mcpro.2023.100520] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 02/18/2023] [Accepted: 02/22/2023] [Indexed: 02/28/2023] Open
Abstract
Ovarian cancer is a gynecological tumor with extremely high mortality and poor prognosis. Exosomes derived from tumor cells contain abundant proteins that may influence tumor metastasis. The purpose of our study was to explore the proteomic profile of serum exosomes from Epithelial ovarian cancer (EOC) patients and to find potential diagnostic markers for EOC. We obtained purified exosomes from serum using ultracentrifugation. Migration assay was used to evaluate the effects of exosomes on the migration of EOC cells. Proteomic profile of serum exosomes was analyzed by Liquid chromatogram-tande mass spectrometry (LC-MS/MS). The level of LRP1 in serum and serum exosomes were determined by Enzyme-Linked Immunosorbent Assay (ELISA). Western blot and Immunohistochemistry were used to determine the level of LRP1 in tissues. Moreover, we performed small-interfering RNA-mediated knockdown of LRP1 in EOC cells to obtain SI-LRP1-Exos and SI-NC-Exos. The detailed mechanisms by which exosomal LRP1 affected the migration of EOC cells in vitro and in vivo were also explored. We found that serum exosomes from EOC patients contributed to the migration of EOC cells. The level of serum exosomal LRP1 of EOC patients was significantly upregulated compared with that of healthy volunteers, which was consistent with the result of ELISA. We found that exosomal LRP1 regulated the expression of MMP2 and MMP9 through ERK signaling pathway and affected the migration of EOC cells in vitro and in vivo. Therefore, we propose that exosomal LRP1 contributes to the migration of EOC and may act as an important diagnostic and prognostic biomarker of EOC.
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Affiliation(s)
- Wei Zhou
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. 221004
| | - Jiachen Ma
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. 221004
| | - Han Zhao
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. 221004
| | - Qing Wang
- Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, China. 221004
| | - Xiaoli Guo
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. 221004
| | - Linna Chen
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. 221004
| | - Zhonghui Cao
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. 221004
| | - Jiahao Xu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. 221004
| | - Bei Zhang
- Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, China. 221004.
| | - Xueyan Zhou
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. 221004.
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30
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Yu J, Ostowari A, Gonda A, Mashayekhi K, Dayyani F, Hughes CCW, Senthil M. Exosomes as a Source of Biomarkers for Gastrointestinal Cancers. Cancers (Basel) 2023; 15:cancers15041263. [PMID: 36831603 PMCID: PMC9954462 DOI: 10.3390/cancers15041263] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/03/2023] [Accepted: 02/06/2023] [Indexed: 02/18/2023] Open
Abstract
Exosomes are small, lipid-bilayer bound extracellular vesicles of 40-160 nanometers in size that carry important information for intercellular communication. Exosomes are produced more by tumor cells than normal cells and carry tumor-specific content, such as DNA, RNA, and proteins, which have been implicated in tumorigenesis, tumor progression, and treatment response. Due to the critical role of exosomes in cancer development and progression, they can be exploited to develop specific biomarkers and therapeutic targets. Since exosomes are present in various biofluids, such as blood, saliva, urine, and peritoneal fluid, they are ideally suited to be developed as liquid biopsy tools for early diagnosis, molecular profiling, disease surveillance, and treatment response monitoring. In the past decade, numerous studies have been published about the functional significance of exosomes in a wide variety of cancers, with a particular focus on exosome-derived RNAs and proteins as biomarkers. In this review, utilizing human studies on exosomes, we highlight their potential as diagnostic, prognostic, and predictive biomarkers in gastrointestinal cancers.
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Affiliation(s)
- Jingjing Yu
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA
| | - Arsha Ostowari
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA
| | - Amber Gonda
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA
| | - Kiarash Mashayekhi
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA
| | - Farshid Dayyani
- Division of Hematology/Oncology, Department of Medicine, University of California, Irvine Medical Center, Orange, CA 92868, USA
| | - Christopher C. W. Hughes
- Department of Molecular Biology & Biochemistry and Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA
| | - Maheswari Senthil
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA
- Correspondence:
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31
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Zhang H, Wang S, Sun M, Cui Y, Xing J, Teng L, Xi Z, Yang Z. Exosomes as smart drug delivery vehicles for cancer immunotherapy. Front Immunol 2023; 13:1093607. [PMID: 36733388 PMCID: PMC9888251 DOI: 10.3389/fimmu.2022.1093607] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 12/23/2022] [Indexed: 01/19/2023] Open
Abstract
Exosomes (Exos) as drug delivery vehicles have been widely used for cancer immunotherapy owing to their good biocompatibility, low toxicity, and low immunogenicity. Some Exos-based cancer immunotherapy strategies such as tuning of immunosuppressive tumor microenvironment, immune checkpoint blockades, and cancer vaccines have also been investigated in recent years, which all showed excellent therapeutic effects for malignant tumor. Furthermore, some Exos-based drug delivery systems (DDSs) for cancer immunotherapy have also undergone clinic trails, indicating that Exos are a promising drug delivery carrier. In this review, in order to promote the development of Exos-based DDSs in cancer immunotherapy, the biogenesis and composition of Exos, and Exos as drug delivery vehicles for cancer immunotherapy are summarized. Meanwhile, their clinical translation and challenges are also discussed. We hope this review will provide a good guidance for Exos as drug delivery vehicles for cancer immunotherapy.
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Affiliation(s)
- Huan Zhang
- School of Life Sciences, Jilin University, Changchun, China
| | - Simiao Wang
- School of Life Sciences, Jilin University, Changchun, China
| | - Man Sun
- School of Life Sciences, Jilin University, Changchun, China
| | - Yaxin Cui
- School of Life Sciences, Jilin University, Changchun, China
| | - Jianming Xing
- School of Life Sciences, Jilin University, Changchun, China
| | - Lesheng Teng
- School of Life Sciences, Jilin University, Changchun, China
| | - Zhifang Xi
- School of Horticulture and Food, Guangdong Eco-Engineering Polytechnic, Guangzhou, China,*Correspondence: Zhifang Xi, ; Zhaogang Yang,
| | - Zhaogang Yang
- School of Life Sciences, Jilin University, Changchun, China,*Correspondence: Zhifang Xi, ; Zhaogang Yang,
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32
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Ma S, Zhou M, Xu Y, Gu X, Zou M, Abudushalamu G, Yao Y, Fan X, Wu G. Clinical application and detection techniques of liquid biopsy in gastric cancer. Mol Cancer 2023; 22:7. [PMID: 36627698 PMCID: PMC9832643 DOI: 10.1186/s12943-023-01715-z] [Citation(s) in RCA: 67] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 01/02/2023] [Indexed: 01/12/2023] Open
Abstract
Gastric cancer (GC) is one of the most common tumors worldwide and the leading cause of tumor-related mortality. Endoscopy and serological tumor marker testing are currently the main methods of GC screening, and treatment relies on surgical resection or chemotherapy. However, traditional examination and treatment methods are more harmful to patients and less sensitive and accurate. A minimally invasive method to respond to GC early screening, prognosis monitoring, treatment efficacy, and drug resistance situations is urgently needed. As a result, liquid biopsy techniques have received much attention in the clinical application of GC. The non-invasive liquid biopsy technique requires fewer samples, is reproducible, and can guide individualized patient treatment by monitoring patients' molecular-level changes in real-time. In this review, we introduced the clinical applications of circulating tumor cells, circulating free DNA, circulating tumor DNA, non-coding RNAs, exosomes, and proteins, which are the primary markers in liquid biopsy technology in GC. We also discuss the current limitations and future trends of liquid biopsy technology as applied to early clinical biopsy technology.
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Affiliation(s)
- Shuo Ma
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Meiling Zhou
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Yanhua Xu
- grid.452743.30000 0004 1788 4869Department of Laboratory Medicine, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225000 Jiangsu China
| | - Xinliang Gu
- grid.440642.00000 0004 0644 5481Department of Laboratory Medicine, Medical School, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001 Jiangsu China
| | - Mingyuan Zou
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Gulinaizhaer Abudushalamu
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Yuming Yao
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Xiaobo Fan
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China
| | - Guoqiu Wu
- grid.452290.80000 0004 1760 6316Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Department of Laboratory Medicine, Medical School of Southeast University, Nanjing, 210009 Jiangsu China ,grid.263826.b0000 0004 1761 0489Jiangsu Provincial Key Laboratory of Critical Care Medicine, Southeast University, Nanjing, 210009 Jiangsu China
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Roshanazadeh MR, Adelipour M, Sanaei A, Chenane H, Rashidi M. TRIM3 and TRIM16 as potential tumor suppressors in breast cancer patients. BMC Res Notes 2022; 15:312. [PMID: 36180926 PMCID: PMC9523982 DOI: 10.1186/s13104-022-06193-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 09/07/2022] [Indexed: 11/10/2022] Open
Abstract
Objective Breast cancer is the leading cause of death among women in many countries. Numerous factors serve as oncogenes or tumor suppressors in breast cancer. The large family of Tripartite-motif (TRIM) proteins with ~ 80 members has drawn attention for their role in cancer. TRIM3 and TRIM16 have shown suppressive activity in different cancers. This study aimed to evaluate the expression of TRIM3 and TRIM16 in cancerous and normal breast samples and to investigate their association with different clinical and pathological parameters. Results qRT-PCR was utilized to determine the gene expression of TRIM3 and TRIM16. The expression of TRIM3 and TRIM16 genes in tumor samples were significantly reduced to 0.45 and 0.29 fold, respectively. TRIM3 and TRIM16 genes expression were both positively correlated with the invasion of breast cancer. TRIM3 gene expression was associated with tumors’ histological grade. However, no significant association was found between the expression of the genes and tumor size, stage and necrosis. The expression of TRIM3 and TRIM16 are significantly reduced in breast cancer tissues. Besides, the expression of both TRIM3 and TRIM16 genes significantly plummet in lymphatic/vascular and perineural invasive samples. Hence, we suggest a potential tumor suppressor role for TRIM3 and TRIM16 in breast cancer.
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Affiliation(s)
- Mohammad Reza Roshanazadeh
- Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of clinical biochemistry, Faculty of medicine, jundishapour University of medical sciences, Ahvaz, Iran
| | - Maryam Adelipour
- Department of clinical biochemistry, Faculty of medicine, jundishapour University of medical sciences, Ahvaz, Iran
| | - Arash Sanaei
- Department of clinical biochemistry, Faculty of medicine, jundishapour University of medical sciences, Ahvaz, Iran
| | - Hadi Chenane
- Department of clinical biochemistry, Faculty of medicine, jundishapour University of medical sciences, Ahvaz, Iran
| | - Mojtaba Rashidi
- Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. .,Department of clinical biochemistry, Faculty of medicine, jundishapour University of medical sciences, Ahvaz, Iran.
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Ma X, Ou K, Liu X, Yang L. Application progress of liquid biopsy in gastric cancer. Front Oncol 2022; 12:969866. [PMID: 36185234 PMCID: PMC9521037 DOI: 10.3389/fonc.2022.969866] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 08/26/2022] [Indexed: 11/13/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors globally. Guiding the individualized treatment of GC is the focus of research. Obtaining representative biological samples to study the biological characteristics of GC is the focus of diagnosis and treatment of GC. Liquid biopsy technology can use high-throughput sequencing technology to detect biological genetic information in blood. Compared with traditional tissue biopsy, liquid biopsy can determine the dynamic changes of tumor. As a noninvasive auxiliary diagnostic method, liquid biopsy can provide diagnostic and prognostic information concerning the progression of the disease. Liquid biopsy includes circulating tumor cells, circulating tumor DNA, circulating tumor RNA, tumor educated platelets, exosomes, and cytokines. This article describes the classification of liquid biopsy and its application value in the occurrence, development, and therapeutic efficacy of GC.
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Yi X, Chen J, Huang D, Feng S, Yang T, Li Z, Wang X, Zhao M, Wu J, Zhong T. Current perspectives on clinical use of exosomes as novel biomarkers for cancer diagnosis. Front Oncol 2022; 12:966981. [PMID: 36119470 PMCID: PMC9472136 DOI: 10.3389/fonc.2022.966981] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 08/01/2022] [Indexed: 12/11/2022] Open
Abstract
Exosomes are a heterogeneous subset of extracellular vesicles (EVs) that biogenesis from endosomes. Besides, exosomes contain a variety of molecular cargoes including proteins, lipids and nucleic acids, which play a key role in the mechanism of exosome formation. Meanwhile, exosomes are involved with physiological and pathological conditions. The molecular profile of exosomes reflects the type and pathophysiological status of the originating cells so could potentially be exploited for diagnostic of cancer. This review aims to describe important molecular cargoes involved in exosome biogenesis. In addition, we highlight exogenous factors, especially autophagy, hypoxia and pharmacology, that regulate the release of exosomes and their corresponding cargoes. Particularly, we also emphasize exosome molecular cargoes as potential biomarkers in liquid biopsy for diagnosis of cancer.
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Affiliation(s)
- Xiaomei Yi
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jie Chen
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Defa Huang
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Shuo Feng
- English Teaching and Research Section, Gannan Healthcare Vocational College, Ganzhou, China
| | - Tong Yang
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Zhengzhe Li
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Xiaoxing Wang
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Minghong Zhao
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jiyang Wu
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Tianyu Zhong
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- *Correspondence: Tianyu Zhong,
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Wang S, He Y, Lu J, Wang Y, Wu X, Yan G, Fang X, Liu B. All-in-One Strategy for Downstream Molecular Profiling of Tumor-Derived Exosomes. ACS APPLIED MATERIALS & INTERFACES 2022; 14:36341-36352. [PMID: 35916896 DOI: 10.1021/acsami.2c07143] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
In light of the significance of exosomes in cancer diagnosis and treatment, it is important to understand the components and functions of exosomes. Herein, an all-in-one strategy has been proposed for comprehensive characterization of exosomal proteins based on nanoporous TiO2 clusters acting as both an extractor for exosome isolation and a nanoreactor for downstream molecular profiling. With the improved hydrophilicity and inherent properties of TiO2, exosomes can be captured by a versatile nanodevice through the specific binding and hydrophilicity interaction synergistically. The strong concerted effect between exosomes and nanodevices ensured high efficiency and specificity of exosome isolation with high recovery and low contaminations. Meanwhile, highly efficient downstream proteomic analysis of the purified exosomes was also enabled by the nanoporous TiO2 clusters. Benefiting from the porous structure of the nanodevice, the lysed exosomal proteins are highly concentrated in the nanopore to achieve high-efficiency in situ proteolytic digestion. Therefore, the unique features of the TiO2 clusters ensured that all the complex steps about isolation and analysis of exosomes were completed efficiently in one simple nanodevice. The concept was first proved with exosomes from cell culture medium, where a high number of identified total proteins and protein groups in exosomes were obtained. Taking advantage of these attractive merits, the first example of the integrated platform has been successfully applied to the analysis of exosomes in complex real-case samples. Not only 196 differential protein biomarker candidates were discovered, but also many more significant cellular components and functions related to gastric cancer were found. These results suggest that the nanoporous TiO2 cluster-based all-in-one strategy can serve as a simple, cost-effective, and integrated platform to facilitate comprehensive analysis of exosomes. Such an approach will provide a valuable tool for the study of exosome markers and their functions.
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Affiliation(s)
- Shurong Wang
- Department of Chemistry, Shanghai Stomatological Hospital, School of Pharmacy, Institute of Biomedical Sciences, Fudan University, Shanghai 200438, China
| | - Ying He
- Department of Chemistry, Shanghai Stomatological Hospital, School of Pharmacy, Institute of Biomedical Sciences, Fudan University, Shanghai 200438, China
| | - Jiayin Lu
- Department of Chemistry, Shanghai Stomatological Hospital, School of Pharmacy, Institute of Biomedical Sciences, Fudan University, Shanghai 200438, China
| | - Yuqing Wang
- Department of Chemistry, Shanghai Stomatological Hospital, School of Pharmacy, Institute of Biomedical Sciences, Fudan University, Shanghai 200438, China
| | - Xiaofeng Wu
- Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States
| | - Guoquan Yan
- Department of Chemistry, Shanghai Stomatological Hospital, School of Pharmacy, Institute of Biomedical Sciences, Fudan University, Shanghai 200438, China
| | - Xiaoni Fang
- Department of Chemistry, Shanghai Stomatological Hospital, School of Pharmacy, Institute of Biomedical Sciences, Fudan University, Shanghai 200438, China
| | - Baohong Liu
- Department of Chemistry, Shanghai Stomatological Hospital, School of Pharmacy, Institute of Biomedical Sciences, Fudan University, Shanghai 200438, China
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Mishra LC, Pandey U, Gupta A, Gupta J, Sharma M, Mishra G. Alternating exosomes and their mimetics as an emergent strategy for targeted cancer therapy. Front Mol Biosci 2022; 9:939050. [PMID: 36032679 PMCID: PMC9399404 DOI: 10.3389/fmolb.2022.939050] [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: 05/08/2022] [Accepted: 07/15/2022] [Indexed: 11/18/2022] Open
Abstract
Exosomes, a subtype of the class of extracellular vesicles and nano-sized particles, have a specific membrane structure that makes them an alternative proposition to combat with cancer through slight modification. As constituents of all most all the primary body fluids, exosomes establish the status of intercellular communication. Exosomes have specific proteins/mRNAs and miRNAs which serve as biomarkers, imparting a prognostic tool in clinical and disease pathologies. They have efficient intrinsic targeting potential and efficacy. Engineered exosomes are employed to deliver therapeutic cargos to the targeted tumor cell or the recipient. Exosomes from cancer cells bring about changes in fibroblast via TGFβ/Smad pathway, augmenting the tumor growth. These extracellular vesicles are multidimensional in terms of the functions that they perform. We herein discuss the uptake and biogenesis of exosomes, their role in various facets of cancer studies, cell-to-cell communication and modification for therapeutic and diagnostic use.
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Affiliation(s)
| | - Utkarsh Pandey
- Department of Zoology, Swami Shraddhanand College, University of Delhi, New Delhi, India
| | - Abhikarsh Gupta
- Department of Microbiology, Swami Shraddhanand College, University of Delhi, New Delhi, India
| | - Jyotsna Gupta
- Department of Microbiology, Swami Shraddhanand College, University of Delhi, New Delhi, India
| | - Monal Sharma
- Betterhumans Inc., Gainesville, FL, United States
| | - Gauri Mishra
- Department of Zoology, Swami Shraddhanand College, University of Delhi, New Delhi, India
- Division Radiopharmaceuticals and Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, New Delhi, India
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Skryabin GO, Vinokurova SV, Galetsky SA, Elkin DS, Senkovenko AM, Denisova DA, Komelkov AV, Stilidi IS, Peregorodiev IN, Malikhova OA, Imaraliev OT, Enikeev AD, Tchevkina EM. Isolation and Characterization of Extracellular Vesicles from Gastric Juice. Cancers (Basel) 2022; 14:cancers14143314. [PMID: 35884376 PMCID: PMC9318556 DOI: 10.3390/cancers14143314] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/24/2022] [Accepted: 07/02/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary Gastric cancer (GC) is one of the most common cancers and the fifth leading cause of cancer-related deaths worldwide. The steadily growing interest in secreted extracellular vesicles (EVs) is related to their ability to carry a variety of biologically active molecules, which can be used as markers for liquid noninvasive diagnosis of malignant neoplasms. For these applications, blood is the most widely used source of EVs. However, this body fluid contains an extremely heterogeneous mixture of EVs originating from different types of normal cells and tissues. The aim of this study was to assess the possibility of using gastric juice (GJ) as an alternative source of EVs since it is expected to be enriched in vesicles of tumor origin. We validated the presence of EVs in GJ using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western-blot analysis of exosomal markers, showed for the first time the feasibility of their isolation by ultracentrifugation and demonstrated the prospect of using GJ-derived EVs as a source of GC miRNA markers. Abstract EVs are involved in local and distant intercellular communication and play a vital role in cancer development. Since EVs have been found in almost all body fluids, there are currently active attempts for their application in liquid diagnostics. Blood is the most commonly used source of EVs for the screening of cancer markers, although the percentage of tumor-derived EVs in the blood is extremely low. In contrast, GJ, as a local biofluid, is expected to be enriched with GC-associated EVs. However, EVs from GJ have never been applied for the screening and are underinvestigated overall. Here we show that EVs can be isolated from GJ by ultracentrifugation. TEM analysis showed high heterogeneity of GJ-derived EVs, including those with exosome-like size and morphology. In addition to morphological diversity, EVs from individual GJ samples differed in the composition of exosomal markers. We also show the presence of stomatin within GJ-derived EVs for the first time. The first conducted comparison of miRNA content in EVs from GC patients and healthy donors performed using a pilot sampling revealed the significant differences in several miRNAs (-135b-3p, -199a-3p, -451a). These results demonstrate the feasibility of the application of GJ-derived EVs for screening for miRNA GC markers.
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Affiliation(s)
- Gleb O. Skryabin
- Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (G.O.S.); (S.V.V.); (S.A.G.); (D.S.E.); (D.A.D.); (A.D.E.)
| | - Svetlana V. Vinokurova
- Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (G.O.S.); (S.V.V.); (S.A.G.); (D.S.E.); (D.A.D.); (A.D.E.)
| | - Sergey A. Galetsky
- Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (G.O.S.); (S.V.V.); (S.A.G.); (D.S.E.); (D.A.D.); (A.D.E.)
| | - Danila S. Elkin
- Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (G.O.S.); (S.V.V.); (S.A.G.); (D.S.E.); (D.A.D.); (A.D.E.)
| | - Alexey M. Senkovenko
- Department of Bioengineering, Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, 1/12, 111234 Moscow, Russia;
| | - Darya A. Denisova
- Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (G.O.S.); (S.V.V.); (S.A.G.); (D.S.E.); (D.A.D.); (A.D.E.)
| | - Andrey V. Komelkov
- Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (G.O.S.); (S.V.V.); (S.A.G.); (D.S.E.); (D.A.D.); (A.D.E.)
- Correspondence: (A.V.K.); (E.M.T.)
| | - Ivan S. Stilidi
- Research Institute of Clinical Oncology, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (I.S.S.); (I.N.P.); (O.A.M.); (O.T.I.)
| | - Ivan N. Peregorodiev
- Research Institute of Clinical Oncology, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (I.S.S.); (I.N.P.); (O.A.M.); (O.T.I.)
| | - Olga A. Malikhova
- Research Institute of Clinical Oncology, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (I.S.S.); (I.N.P.); (O.A.M.); (O.T.I.)
| | - Oiatiddin T. Imaraliev
- Research Institute of Clinical Oncology, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (I.S.S.); (I.N.P.); (O.A.M.); (O.T.I.)
| | - Adel D. Enikeev
- Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (G.O.S.); (S.V.V.); (S.A.G.); (D.S.E.); (D.A.D.); (A.D.E.)
| | - Elena M. Tchevkina
- Institute of Carcinogenesis, N. N. Blokhin National Medical Research Center of Oncology, Kashirskoye Sh. 24, 115478 Moscow, Russia; (G.O.S.); (S.V.V.); (S.A.G.); (D.S.E.); (D.A.D.); (A.D.E.)
- Correspondence: (A.V.K.); (E.M.T.)
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Gurudas Shivji G, Dhar R, Devi A. Role of Exosomes and its emerging therapeutic applications in the pathophysiology of Non-Infectious disease. Biomarkers 2022; 27:534-548. [PMID: 35451890 DOI: 10.1080/1354750x.2022.2067233] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
Exosomes are a type of small Extracellular Vesicles (EVs) and play crucial roles in cancer and other diseases. Exosomes role in various diseases has been studied as they regulate intercellular communication and are obtained from almost any part of the body. Exosomes use is complicated in diseases as they promote pathogenesis but also act as a very good therapeutic agent in most diseases. The presence of a complex molecular cargo consisting of nucleic acids (DNA, RNA, miRNA, siRNA, etc.,) makes it a very good delivery agent and acts as a biomarker for many cancers, cardiovascular and neurodegenerative diseases. They can be used to selectively target cells and activate immune cell responses depending on the source obtained. Exosomes based immunotherapy is an area of gaining importance due to the proteins present in them and their specificity to the targeted cells. The role of exosomes in the diagnosis and treatment of non-infectious diseases is discussed in detail in this article.
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Affiliation(s)
- Gauresh Gurudas Shivji
- Cancer Biology and Stem Cell Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Potheri, Kattankulathur, Chengalpattu District, Tamilnadu 603203, India
| | - Rajib Dhar
- Cancer Biology and Stem Cell Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Potheri, Kattankulathur, Chengalpattu District, Tamilnadu 603203, India
| | - Arikketh Devi
- Cancer Biology and Stem Cell Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Potheri, Kattankulathur, Chengalpattu District, Tamilnadu 603203, India
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Xie Y, Yang L, Cao P, Li S, Zhang W, Dang W, Xin S, Jiang M, Xin Y, Li J, Long S, Wang Y, Zhang S, Yang Y, Lu J. Plasma Exosomal Proteomic Pattern of Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis. Front Microbiol 2022; 13:821311. [PMID: 35464963 PMCID: PMC9019563 DOI: 10.3389/fmicb.2022.821311] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 03/07/2022] [Indexed: 11/13/2022] Open
Abstract
Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening syndrome, which is caused by EBV infection that is usually refractory to treatment and shows relapse. The development of new biomarkers for the early diagnosis and clinical treatment of EBV-HLH is urgently needed. Exosomes have been shown to mediate various biological processes and are ideal non-invasive biomarkers. Here, we present the differential plasma exosomal proteome of a patient with EBV-HLH before vs. during treatment and with that of his healthy twin brother. A tandem mass tag-labeled LC-MS technique was employed for proteomic detection. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that differential proteomic profiles were related to virus infection, coagulopathy, nervous system dysfunction, imbalance of immune response, and abnormal liver function. The candidate biomarkers were first identified in the patient’s plasma exosomes at different treatment and follow-up time points. Then, 14 additional EBV-HLH exosome samples were used to verify six differentially expressed proteins. The upregulation of C-reactive protein, moesin, galectin three-binding protein, and heat shock cognate 71 kDa protein and the downregulation of plasminogen and fibronectin 1 could serve as potential biomarkers of EBV-HLH. This plasma exosomal proteomic analysis provides new insights into the diagnostic and therapeutic biomarkers of EBV-HLH.
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Affiliation(s)
- Yan Xie
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Li Yang
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Pengfei Cao
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Shen Li
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Wentao Zhang
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Wei Dang
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Shuyu Xin
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Mingjuan Jiang
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Yujie Xin
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Jing Li
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Sijing Long
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Yiwei Wang
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Senmiao Zhang
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Yang Yang
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
| | - Jianhong Lu
- Department of Hematology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, China
- National Healthcare Commission (NHC) Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China
- China-Africa Research Center of Infectious Diseases, Central South University, Changsha, China
- *Correspondence: Jianhong Lu,
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Islam Khan MZ, Tam SY, Law HKW. Advances in High Throughput Proteomics Profiling in Establishing Potential Biomarkers for Gastrointestinal Cancer. Cells 2022; 11:973. [PMID: 35326424 PMCID: PMC8946849 DOI: 10.3390/cells11060973] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 03/05/2022] [Accepted: 03/08/2022] [Indexed: 12/24/2022] Open
Abstract
Gastrointestinal cancers (GICs) remain the most diagnosed cancers and accounted for the highest cancer-related death globally. The prognosis and treatment outcomes of many GICs are poor because most of the cases are diagnosed in advanced metastatic stages. This is primarily attributed to the deficiency of effective and reliable early diagnostic biomarkers. The existing biomarkers for GICs diagnosis exhibited inadequate specificity and sensitivity. To improve the early diagnosis of GICs, biomarkers with higher specificity and sensitivity are warranted. Proteomics study and its functional analysis focus on elucidating physiological and biological functions of unknown or annotated proteins and deciphering cellular mechanisms at molecular levels. In addition, quantitative analysis of translational proteomics is a promising approach in enhancing the early identification and proper management of GICs. In this review, we focus on the advances in mass spectrometry along with the quantitative and functional analysis of proteomics data that contributes to the establishment of biomarkers for GICs including, colorectal, gastric, hepatocellular, pancreatic, and esophageal cancer. We also discuss the future challenges in the validation of proteomics-based biomarkers for their translation into clinics.
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Affiliation(s)
| | | | - Helen Ka Wai Law
- Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China; (M.Z.I.K.); (S.Y.T.)
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Araujo-Abad S, Saceda M, de Juan Romero C. Biomedical application of small extracellular vesicles in cancer treatment. Adv Drug Deliv Rev 2022; 182:114117. [PMID: 35065142 DOI: 10.1016/j.addr.2022.114117] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 12/09/2021] [Accepted: 01/15/2022] [Indexed: 12/17/2022]
Abstract
Extracellular vesicles (EVs) are produced by almost all cell types in vivo or in vitro. Among them, exosomes are small nanovesicles with a lipid bilayer, proteins and RNAs actively involved in cellular communication, suggesting that they may be used both as biomarkers and for therapeutic purposes in diseases such as cancer. Moreover, the idea of using them as drug delivery vehicle arises as a promising field of study. Here, we reviewed recent findings showing the importance of EVs, with special focus in exosomes as biomarkers including the most relevant proteins found in different cancer types and it is discussed the FDA approved tests which use exosomes in clinical practice. Finally, we present an overview of the different chimeric EVs developed in the last few years, demonstrating that they can be conjugate to nanoparticles, biomolecules, cancer drugs, etc., and can be developed for a specific cancer treatment. Additionally, we summarized the clinical trials where EVs are used in the treatment of several cancer types aiming to improve the prognosis of these deadly diseases.
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Affiliation(s)
- Salome Araujo-Abad
- Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Avda, Universidad s/n, Ed. Torregaitán, Elche, 03202 Alicante, Spain; Centro de Biotecnología, Universidad Nacional de Loja, Avda. Pio Jaramillo Alvarado s/n, Loja, 110111 Loja, Ecuador
| | - Miguel Saceda
- Unidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l'Almazara 11, Elche, 03203 Alicante, Spain; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Avda, Universidad s/n, Ed. Torregaitán, Elche, 03202 Alicante, Spain
| | - Camino de Juan Romero
- Unidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l'Almazara 11, Elche, 03203 Alicante, Spain; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Avda, Universidad s/n, Ed. Torregaitán, Elche, 03202 Alicante, Spain
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43
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Chen W, Li G, Li Z, Zhu J, Wei T, Lei J. Evaluation of plasma exosomal miRNAs as potential diagnostic biomarkers of lymph node metastasis in papillary thyroid carcinoma. Endocrine 2022; 75:846-855. [PMID: 34854020 DOI: 10.1007/s12020-021-02949-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 11/15/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE The early diagnosis of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is clinically important, as it can aid in treatment decision-making and improve prognosis. In the present study, we aimed to identify whether plasma exosomal miRNAs could be potential diagnostic markers of LNM in PTC. METHODS Profiles of plasma exosomal miRNAs were screened using miRNA microarrays. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed in the validation and diagnostic sets to select candidate exosomal miRNAs. Finally, receiver operating characteristic (ROC) curves were generated to evaluate the efficiency of target exosomal miRNAs in distinguishing PTC-N1 patients from PTC-N0 patients. RESULTS In total, 197 miRNAs were found to be differentially expressed in the testing set. Based on the qRT-PCR results, the expression of miR-6774-3p (p < 0.001) and miR-6879-5p (p < 0.001) in the PTC-N1 patients was significantly higher than that in the controls. The AUC values of plasma exosomal miR-6774-3p (0.802; 95% CI, 0.724-0.879) and miR-6879-5p (0.787; 95% CI, 0.706-0.867) and their combination (0.914; 95% CI, 0.865-0.962) were higher than those of the total miRNAs directly isolated from plasma. Moreover, the expression of exosomal miRNAs was stable after treatment with RNase A, prolonged incubation, or repeated freezing and thawing. CONCLUSIONS The two plasma exosomal miRNAs (miR-6774-3p and miR-6879-5p) and their combination could serve as new promising biomarkers for the diagnosis of LNM in PTC patients.
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Affiliation(s)
- Wenjie Chen
- Thyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, 610041, China
- Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Genpeng Li
- Thyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Zhihui Li
- Thyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Jingqiang Zhu
- Thyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Tao Wei
- Thyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, 610041, China
| | - Jianyong Lei
- Thyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, 610041, China.
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Zhang AZ, Yuan X, Liang WH, Zhang HJ, Li Y, Xie YF, Li JF, Jiang CH, Li FP, Shen XH, Pang LJ, Zou H, Zhou WH, Li F, Hu JM. Immune Infiltration in Gastric Cancer Microenvironment and Its Clinical Significance. Front Cell Dev Biol 2022; 9:762029. [PMID: 35252217 PMCID: PMC8893596 DOI: 10.3389/fcell.2021.762029] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 12/30/2021] [Indexed: 12/12/2022] Open
Abstract
Immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer (GC). The research on tumor infiltrating immune cells (TIICs) and immune-related genes in the tumor microenvironment (TME) greatly encourages the development of immunotherapy. The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 TIICs based on gene expression profiles of GC tissues, which were downloaded from TCGA and GEO. TCGA was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes. We have observed the enrichment of multiple TIICs in microenvironment of GC. Some of these cells were closely related to tumor mutational burden (TMB), microsatellite instability (MSI), Fuhrman grade, and TNM staging. Survival analysis showed that the infiltration level of CD8+ T cells, activated CD4+ memory T cells and M2 macrophages were significantly related to the prognosis of GC patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules. The expression levels of CALCR and PTH1R are strikingly related to the expression of immune checkpoint and the prognosis of GC patients. The type and number of TIICs in microenvironment of GC, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment.
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Affiliation(s)
- An Zhi Zhang
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
- Department of Pathology, Jiaxing University Affiliated Women and Children Hospital (Jiaxing Maternity and Child Health Care Hospital), Jiaxing University, Jiaxing, China
| | - Xin Yuan
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Wei Hua Liang
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Hai Jun Zhang
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Ya Li
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Yu Fang Xie
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Jiang Fen Li
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Chen Hao Jiang
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Fan Ping Li
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Xi Hua Shen
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Li Juan Pang
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Hong Zou
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
| | - Wen Hu Zhou
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
| | - Feng Li
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
- Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jian Ming Hu
- Department of Pathology/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China
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Chen L, Wang L, Zhu L, Xu Z, Liu Y, Li Z, Zhou J, Luo F. Exosomes as Drug Carriers in Anti-Cancer Therapy. Front Cell Dev Biol 2022; 10:728616. [PMID: 35155421 PMCID: PMC8826094 DOI: 10.3389/fcell.2022.728616] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 01/04/2022] [Indexed: 12/18/2022] Open
Abstract
Over the years, there has been a high demand for developing new safe and effective drug carriers for cancer therapy. Emerging studies have indicated that exosomes can serve as potent therapeutic carriers since they offer low immunogenicity, high stability, innate and acquired targetability, and the stimulation of anti-cancer immune responses. Yet, the development of exosome-based drug delivery systems remains challenging due to their heterogeneity, low yield, and limited drug loading efficiency. Herein, we summarized the current application of exosomes derived from different cells as drug carriers in anti-cancer therapy in vitro and in vivo. We also discussed the challenges and prospects of exosome-based drug delivery systems in cancer therapy.
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Affiliation(s)
- Lan Chen
- Lung Cancer Center, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Li Wang
- Lung Cancer Center, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Li Wang, ; Jin Zhou, ; Feng Luo,
| | - Lingling Zhu
- Lung Cancer Center, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Zihan Xu
- Lung Cancer Center, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Yanyang Liu
- Lung Cancer Center, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Zhixi Li
- Lung Cancer Center, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Jin Zhou
- School of Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China
- *Correspondence: Li Wang, ; Jin Zhou, ; Feng Luo,
| | - Feng Luo
- Lung Cancer Center, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
- *Correspondence: Li Wang, ; Jin Zhou, ; Feng Luo,
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46
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Su H, Ren W, Zhang D. Research progress on exosomal proteins as diagnostic markers of gastric cancer (review article). Clin Exp Med 2022; 23:203-218. [DOI: 10.1007/s10238-022-00793-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 01/04/2022] [Indexed: 12/20/2022]
Abstract
AbstractGastric cancer (GC) is one of the most common types of tumors and the most common cause of cancer mortality worldwide. The diagnosis of GC is critical to its prevention and treatment. Available tumor markers are the crucial step for GC diagnosis. Recent studies have shown that proteins in exosomes are potential diagnostic and prognostic markers for GC. Exosomes, secreted by cells, are cup-shaped with a diameter of 30–150 nm under the electron microscope. They are also surrounded by lipid bilayers and are widely found in various body fluids. Exosomes contain proteins, lipids and nucleic acid. The examination of exosomal proteins has the advantages of quickness, easy sampling, and low pain and cost, as compared with the routine inspection method of GC, which may lead to marked developments in GC diagnosis. This article summarized the exosomal proteins with a diagnostic and prognostic potential in GC, as well as exosomal proteins involved in GC progression.
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Cheng H, Yang Q, Wang R, Luo R, Zhu S, Li M, Li W, Chen C, Zou Y, Huang Z, Xie T, Wang S, Zhang H, Tian Q. Emerging Advances of Detection Strategies for Tumor-Derived Exosomes. Int J Mol Sci 2022; 23:ijms23020868. [PMID: 35055057 PMCID: PMC8775838 DOI: 10.3390/ijms23020868] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 01/06/2022] [Accepted: 01/11/2022] [Indexed: 12/12/2022] Open
Abstract
Exosomes derived from tumor cells contain various molecular components, such as proteins, RNA, DNA, lipids, and carbohydrates. These components play a crucial role in all stages of tumorigenesis and development. Moreover, they reflect the physiological and pathological status of parental tumor cells. Recently, tumor-derived exosomes have become popular biomarkers for non-invasive liquid biopsy and the diagnosis of numerous cancers. The interdisciplinary significance of exosomes research has also attracted growing enthusiasm. However, the intrinsic nature of tumor-derived exosomes requires advanced methods to detect and evaluate the complex biofluid. This review analyzes the relationship between exosomes and tumors. It also summarizes the exosomal biological origin, composition, and application of molecular markers in clinical cancer diagnosis. Remarkably, this paper constitutes a comprehensive summary of the innovative research on numerous detection strategies for tumor-derived exosomes with the intent of providing a theoretical basis and reference for early diagnosis and clinical treatment of cancer.
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Affiliation(s)
- Huijuan Cheng
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Qian Yang
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Rongrong Wang
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Ruhua Luo
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Shanshan Zhu
- Public Health Institutes, Hangzhou Normal University, Hangzhou 311121, China;
| | - Minhui Li
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Wenqi Li
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Cheng Chen
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Yuqing Zou
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Zhihua Huang
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Tian Xie
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
| | - Shuling Wang
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Correspondence: (S.W.); (H.Z.); (Q.T.)
| | - Honghua Zhang
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Correspondence: (S.W.); (H.Z.); (Q.T.)
| | - Qingchang Tian
- College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; (H.C.); (Q.Y.); (R.W.); (R.L.); (M.L.); (W.L.); (C.C.); (Y.Z.); (Z.H.); (T.X.)
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Hangzhou Normal University, Hangzhou 311121, China
- Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Correspondence: (S.W.); (H.Z.); (Q.T.)
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Wang F, Wang W, Wu X, Tang C, Du F, Lu Z, Zhang Z, Xu H, Cao X, Li PA. Downregulation of TRIM33 Promotes Survival and Epithelial-Mesenchymal Transition in Gastric Cancer. Technol Cancer Res Treat 2022; 21:15330338221114505. [PMID: 35929141 PMCID: PMC9358585 DOI: 10.1177/15330338221114505] [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] [Indexed: 12/24/2022] Open
Abstract
Among all malignancies worldwide, gastric cancer is the fifth most common cancer with the third highest mortality rate. One of the main reasons for the low survival rate is the recurrence and metastasis that occurs in many patients after surgery. Numerous studies have shown that abnormal TRIM33 expression is associated with the progression of malignant tumors. TRIM33 can function either as a tumor suppressor or tumor promoter in different cancers. Our data showed that TRIM33 was highly expressed in stomach cancer, and in human gastric cancer tissues, low expression of TRIM33 was associated with poor prognosis in patients with gastric cancer. To clarify the function of TRIM33 in survival and epithelial–mesenchymal transition in gastric cancer cells, we investigated the effect of TRIM33 knockdown in several gastric cancer cell lines. Downregulation of TRIM33 in BGC-823 and SGC-7901 cells enhanced the proliferation, colony formation, and migratory ability of these gastric cancer cells. It also promoted epithelial–mesenchymal transition; transfection of cells with siRNA targeting TRIM33 led to the upregulation of vimentin and N-Cadherin expression, and downregulation of E-Cadherin expression. Meanwhile, the transforming growth factor beta pathway was activated: levels of transforming growth factor beta were elevated and the expressions of p-Smad2, Smad2, Smad3, and Smad4 were activated. To confirm the role of TRIM33 in vivo, a xenograft model was established in nude mice. Immunohistochemical analysis identified that the protein levels of TRIM33, p-Smad2, Smad2, Smad3, Smad4, vimentin, and N-Cadherin were increased, and E-Cadherin levels were decreased, in xenograft tumors from the si-TRIM33 group. Taken together, these results suggest that TRIM33 may be a potential marker for the diagnosis and prognosis of gastric cancer. Furthermore, it may also serve as a novel target for gastric cancer treatment.
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Affiliation(s)
- Fang Wang
- Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Wenjun Wang
- Department of Pathology, Basic Medical School, 105002Ningxia Medical University, Yinchuan, China
| | - Xiaoting Wu
- Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Cui Tang
- Department of Pathology, Basic Medical School, 105002Ningxia Medical University, Yinchuan, China
| | - Fang Du
- School of Information Engineering, 56693Ningxia University, Ningxia, China
| | - Zhiguo Lu
- Department of Pediatric Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Zhuoyang Zhang
- Department of Pathology, Basic Medical School, 105002Ningxia Medical University, Yinchuan, China
| | - Hui Xu
- Department of Pathology, Basic Medical School, 105002Ningxia Medical University, Yinchuan, China
| | - Xiangmei Cao
- Department of Pathology, Basic Medical School, 105002Ningxia Medical University, Yinchuan, China
| | - P Andy Li
- Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), North Carolina Central University, Durham, NC, USA
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Wang S, Chen X, Fu Y, Zhang H, Liu W, Song X, Ma X, Cheng S, Lu J. Relationship of ERCC5 genetic polymorphisms with metastasis and recurrence of gastric cancer. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2021; 67:1538-1543. [PMID: 34909875 DOI: 10.1590/1806-9282.20210209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 09/07/2021] [Indexed: 11/22/2022]
Abstract
OBJECTIVE This study aims to explore the role of ERCC5 genetic polymorphisms in gastric cancer and their relationship with metastasis and recurrence of gastric cancer. METHODS A total of 200 patients with gastric cancer and 133 healthy subjects were enrolled. MassARRAY iPLEX® technology was used to genotype ERCC5 rs2016073, rs751402, rs2094258, rs2296147, and rs2296148 between the control group and the gastric cancer group. The relationship of ERCC5 genetic polymorphisms with metastasis and recurrence of gastric cancer was explored. The differences in sociodemographic characteristics between patients with gastric cancer and control subjects were compared using the chi-square test. The genetic loci between the control group and the gastric cancer group were analyzed by the chi-square test. RESULTS There was no significant difference in the metastasis of gastric cancer between males and females (p=0.628), but there was a significant difference in the metastasis of gastric cancer (p=0.005). Patients aged ≤60 years and >60 years showed no significant difference in the metastasis of gastric cancer (p=0.420), but there was a significant difference in the recurrence of gastric cancer (p<0.001). The loci rs2016073, rs751402, and rs2094258 in the gastric cancer group showed no significant differences compared with the control group (p=0.194), and the loci rs2296147 and rs2296148 showed significant differences. CONCLUSIONS The results suggested that ERCC5 polymorphisms (e.g., rs201607, rs751402, rs2094258, rs2296147, and rs2296148) may be associated with metastasis and recurrence of gastric cancer.
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Affiliation(s)
- Shulan Wang
- Gansu Provincial Hospital, Department of Digestive - Lanzhou (Gansu) China
| | - Xiang Chen
- Gansu Provincial Hospital, Department of Digestive - Lanzhou (Gansu) China
| | - Yingming Fu
- Wushan County Hospital, Department of Digestive - Tianshui (Gansu), China
| | - Huiqin Zhang
- Gansu Provincial Hospital, Department of Digestive - Lanzhou (Gansu) China
| | - Wenwen Liu
- Gansu Provincial Hospital, Department of Digestive - Lanzhou (Gansu) China
| | - Xuejuan Song
- Gansu Provincial Hospital, Department of Digestive - Lanzhou (Gansu) China
| | - Xin Ma
- Gansu Provincial Hospital, Department of Digestive - Lanzhou (Gansu) China
| | - Sha Cheng
- Gansu Provincial Hospital, Department of Digestive - Lanzhou (Gansu) China
| | - Juanjuan Lu
- Gansu Provincial Hospital, Department of Digestive - Lanzhou (Gansu) China
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Tripartite Motif Containing 3 inhibits the aggressive behaviors of papillary thyroid carcinoma and indicates lower recurrence risk. Genes Genomics 2021; 44:455-465. [PMID: 34860317 DOI: 10.1007/s13258-021-01197-7] [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: 07/21/2021] [Accepted: 11/22/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Tripartite Motif Containing 3 (TRIM3) has been reported to be downregulated in several malignancies. However, its prognostic significance in thyroid cancer remains unknown. OBJECTIVE Here we aimed to investigate TRIM3's expression and its involvement in papillary thyroid carcinoma (PTC). METHODS Clinicopathological analyses were performed in patients with PTC. Expression of TRIM3 protein was evaluated by IHC. The prognostic role of TRIM3 in PTC patients was assessed by univariate and multivariate analyses. Cell proliferation and invasion were tested in two PTC cell lines following overexpression or knockdown. RESULTS TRIM3 was decreased in PTC tissues compared to adjacent thyroid tissues on both mRNA and protein levels. Additionally, low expression of TRIM3 was significantly related to tumor size, lymph node metastasis and TNM stage. Moreover, TRIM3 was identified as an independent prognosis factor by multivariate analysis. Cellular data revealed that TRIM3 can inhibit the proliferation and invasion of PTC cells. Consistently, TRIM3 can upregulate the expression level of E-cadherin, while downregulate N-cadherin, Vimentin, and cyclin D1 expression. CONCLUSIONS TRIM3 expression was downregulated in PTC tissues comparing with that in adjacent nontumorous thyroid tissues. Lower TRIM3 expression in PTC can contribute independently to a poorer prognosis by enhancing PTC proliferation and invasion, highlighting its potential as a novel therapeutic target and prognostic biomarker.
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