NASH 诱导的肝硬化合并肝细胞癌中的潜在生物标志物：外泌体 miR-182、miR-301a 和 miR-373 作用的初步研究
Potential biomarkers in NASH-induced liver cirrhosis with hepatocellular carcinoma: A preliminary work on roles of exosomal miR-182, miR-301a, and miR-373.
机构信息
Universiti Kebangsaan Malaysia, Faculty of Medicine, Department of Physiology, kuala Lumpur, Malaysia.
出版信息
Malays J Pathol. 2020 Dec;42(3):377-384.
INTRODUCTION
Recent studies have published the roles of exosomal miRNAs in the pathogenesis of various type of malignancies and can be developed as potential biomarkers for diagnostic, prognostic and therapeutic purposes. The aim of this study was to identify the expression level of selected miRNAs (miR-182, miR-301a, and miR-373) in exosomes of the serum and ascitic fluid in patients with non-alcoholic steatohepatitis (NASH)-related liver cirrhosis with or without hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
A literature search was performed to identify potential miRNAs involved in the pathogenesis of HCC. Unpaired serum and ascitic fluid were obtained from 52 patients with NASH related liver cirrhosis (n=26 for each group of with and without HCC). Exosomal miRNA was isolated from all samples. Expression levels of miR-182, miR-301a and miR- 373 were determined using quantitative real-time PCR.
RESULTS
Serum-derived exosomal mir-182, miR-301a and miR-373 were significantly up-regulated with fold change of 1.77, 2.52, and 1.67 (p< 0.05) respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC. We identified the expression levels of ascitic fluid-derived exosomal mir-182, miR-301a, and miR-373 were significantly up-regulated with fold change of 1.6, 1.94 and 2.13 respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC (p <0.05). There was poor correlation expression of all the selected exosomal miRNA between serum- and ascitic fluid-derived in HCC group.
CONCLUSIONS
This preliminary data showed significant increase in the expression levels of exosomal miR-182, miR-301a and miR- 373 in both serum and ascetic fluid suggesting the possible roles of these miRNAs as circulating biomarkers for NASH-induced liver cirrhosis with hepatocellular carcinoma.
简介
最近的研究已经发表了外泌体 miRNAs 在各种类型恶性肿瘤发病机制中的作用，并可以作为诊断、预后和治疗目的的潜在生物标志物进行开发。本研究的目的是确定非酒精性脂肪性肝炎（NASH）相关肝硬化伴或不伴肝细胞癌（HCC）患者血清和腹水中外泌体中选定 miRNAs（miR-182、miR-301a 和 miR-373）的表达水平。
材料和方法
进行文献检索以确定与 HCC 发病机制相关的潜在 miRNAs。从 52 例 NASH 相关肝硬化患者（每组 26 例伴或不伴 HCC）中获得未配对的血清和腹水。从所有样本中分离外泌体 miRNA。使用定量实时 PCR 测定 miR-182、miR-301a 和 miR-373 的表达水平。
结果
与 NASH 诱导的无 HCC 肝硬化相比，NASH 诱导的 HCC 肝硬化患者血清来源的外泌体 miR-182、miR-301a 和 miR-373 的表达分别上调 1.77、2.52 和 1.67 倍（p<0.05）。我们发现腹水来源的外泌体 miR-182、miR-301a 和 miR-373 的表达水平在 NASH 诱导的 HCC 肝硬化患者中分别上调 1.6、1.94 和 2.13 倍（p<0.05）。与 NASH 诱导的无 HCC 肝硬化相比，HCC 组血清和腹水来源的所有选定外泌体 miRNA 的表达均呈低度相关。
结论
本初步数据显示，血清和腹水中外泌体 miR-182、miR-301a 和 miR-373 的表达水平显着升高，提示这些 miRNA 可能作为 NASH 诱导的 HCC 的循环生物标志物。
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