Cell Biology and Genetics Department of Shantou University Medical College, Shantou, China.
The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Microb Pathog. 2017 Nov;112:320-326. doi: 10.1016/j.micpath.2017.10.003. Epub 2017 Oct 6.
Hepatitis C virus (HCV) genotype exerts a major influence on therapeutic response; however, the underlying mechanisms remain unclear. The aim of the study is to investigate the circulating microRNAs as the biomarkers to predict the response to therapy in chronic hepatitisC patients (HepC) with different genotypes.
HepC patients were separated into 4 groups by genotype, healthy individuals were enrolled as the control. microRNA-122 (miR-122), microRNA-155 (miR-155) and HCV RNA in serum and exosome were measured, associations between microRNAs, viral load and other conventional biomarkers were analyzed.
Serum and exosomal HCV RNA in genotype 6a group was highest, followed by genotype 3a/2a, and in genotype 1b were the lowest. The significant correlations existed between exosomal HCV RNA and serum HCVRNA. MiR-122, both in serum (miR-122ser) and in exosome (miR-122exo), was higher in normal control than in HCV group. Specifically, miR-122exo were significantly higher in genotype 1b than other genotype groups (p < 0.05). On the contrary, miR-155exowas significantly lower in genotype 1b than in other groups (p < 0.05 for both). A strongly positive association was found between miR-122/155 and HCV viral load in patients with various genotypes. Higher miR-122ser at the start of therapy predicts a better outcome.
Expression of miR-122/155 differ in each genotypes, miR-122ser could be independent factor affecting the therapy efficacy, which had higher diagnostic value in predicting HCV outcome.
丙型肝炎病毒（HCV）基因型对治疗反应有重大影响；然而，其潜在机制尚不清楚。本研究旨在探讨循环 microRNA 作为生物标志物，预测不同基因型慢性丙型肝炎（HepC）患者对治疗的反应。
根据基因型将 HepC 患者分为 4 组，健康个体作为对照组。检测血清和外泌体中的 microRNA-122（miR-122）、microRNA-155（miR-155）和 HCV RNA，分析 microRNAs 与病毒载量和其他常规生物标志物之间的相关性。
基因型 6a 组血清和外泌体 HCV RNA 最高，基因型 3a/2a 次之，基因型 1b 最低。外泌体 HCV RNA 与血清 HCV RNA 之间存在显著相关性。miR-122，无论是在血清（miR-122ser）还是外泌体（miR-122exo）中，在正常对照组均高于 HCV 组。具体而言，miR-122exo 在基因型 1b 中明显高于其他基因型组（p < 0.05）。相反，miR-155exo 在基因型 1b 中明显低于其他组（p < 0.05）。在不同基因型的患者中，miR-122/155 与 HCV 病毒载量之间存在强烈的正相关。治疗开始时 miR-122ser 水平较高预示着更好的结果。
miR-122/155 的表达在各基因型中存在差异，miR-122ser 可能是影响治疗效果的独立因素，其在预测 HCV 结局方面具有更高的诊断价值。
