Discovery of extracellular vesicle-delivered miR-185-5p in the plasma of patients as an indicator for advanced adenoma and colorectal cancer

Journal of Translational Medicine

Research

Hao Wang¹  Pi-Qing Gong²  Yun-Jie Shi³  Zhi-Qian Hu⁴  Qiang Sun⁵  Xin-Xing Li⁶  Fang-Qi Guo⁷  Wei-Ping Chen⁸  Chun-Mei Li⁸  Tong-Guan Tian⁹  Yu-Xiang Fang^1,10 

[1] Department of Anorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 200433, Shanghai, China;Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), 200003, Shanghai, China;Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), 200003, Shanghai, China;Department of Anorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), 200433, Shanghai, China;Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), 200003, Shanghai, China;Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, 200065, Shanghai, China;Department of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), 200003, Shanghai, China;Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, 200065, Shanghai, China;Department of Ultrasound, Shanghai Fourth People’ Hospital, School of Medicine, Tongji University, Shanghai, China;Institute of Basic Medicine and Cancer (IBMC), Zhejiang Cancer Hospital, Chinese Academy of Sciences, 310022, Hangzhou, Zhejiang, China;Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, 200120, Shanghai, China;State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China;

关键词: Extracellular vesicle;    microRNA;    Colorectal advanced adenoma;    Colorectal cancer;    Liquid biopsy;   

DOI  :  10.1186/s12967-023-04249-6

 received in 2023-03-29, accepted in 2023-06-05,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundWe aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC).MethodsWe detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays.ResultsWe screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC.ConclusionEV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC.Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).

【 授权许可】

CC BY   
© The Author(s) 2023

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