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血浆衍生外泌体的 microRNA 图谱及其作为华支睾吸虫相关性胆管癌生物标志物的潜力。

microRNA profiling of exosomes derived from plasma and their potential as biomarkers for Opisthorchis viverrini-associated cholangiocarcinoma.

机构信息

Department of Radiological technology, Faculty of Science, Ramkhamhaeng University, Bangkok, 10240, Thailand; Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

出版信息

Acta Trop. 2024 Oct;258:107362. doi: 10.1016/j.actatropica.2024.107362. Epub 2024 Aug 14.

DOI:10.1016/j.actatropica.2024.107362
PMID:39151716
Abstract

Cholangiocarcinoma (CCA) is a life-threatening disease that impacts patients worldwide. In Southeast Asian countries, the liver fluke Opisthorchis viverrini plays a major role in inducing carcinogenesis of the bile ducts. Due to its asymptomatic nature, O. viverrini infections are rarely treated, consequently leading to the development of advanced stages of CCA before diagnosis. Despite the current use of exosomal microRNAs (miRNA) as diagnostic biomarkers for the early detection of many types of cancer, the applications for miRNA remain limited with CCA. Circulating exosomes, membranous vesicles essential for intercellular communication, were found to contain unique miRNA. In this study, we conducted next-generation sequencing (Ion Torrent PGM) and bioinformatics to characterize and compare the contents of exosomal miRNA derived from the plasma of CCA patients, O. viverrini-infected patients, and healthy individuals, as well as to identify and validate key molecules as markers for screening the diagnosis of CCA and O. viverrini infection. The obtained results showed the success of using NGS technology in discovering exosomal miRNAs, specifically miR-194-5p and miR-192-5p, both of which were upregulated in the O. viverrini-infected group. Interestingly, miR-192-5p was upregulated while miR-194-5p was downregulated in CCA, suggesting their potential use as biomarkers for screening CCA and O. viverrini infection, especially in O. viverrini-endemic areas.

摘要

胆管癌(CCA)是一种危及生命的疾病,影响着全球的患者。在东南亚国家,肝吸虫华支睾吸虫在胆管癌的致癌作用中起主要作用。由于其无症状的性质,华支睾吸虫感染很少得到治疗,因此在诊断前导致 CCA 的晚期发展。尽管目前将外泌体 microRNAs(miRNA)用作许多类型癌症的早期检测的诊断生物标志物,但 miRNA 在 CCA 中的应用仍然有限。循环外泌体是细胞间通讯所必需的膜囊泡,被发现含有独特的 miRNA。在这项研究中,我们进行了下一代测序(Ion Torrent PGM)和生物信息学分析,以表征和比较源自 CCA 患者、华支睾吸虫感染患者和健康个体血浆的外泌体 miRNA 的内容,并鉴定和验证关键分子作为筛查 CCA 和华支睾吸虫感染的诊断标志物。结果表明,NGS 技术在发现外泌体 miRNA 方面取得了成功,特别是 miR-194-5p 和 miR-192-5p,它们在华支睾吸虫感染组中均上调。有趣的是,miR-192-5p 在 CCA 中上调,而 miR-194-5p 下调,表明它们可能用作筛查 CCA 和华支睾吸虫感染的生物标志物,特别是在华支睾吸虫流行地区。

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