Internal Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Mol Cell Biochem. 2018 Oct;447(1-2):125-136. doi: 10.1007/s11010-018-3298-8. Epub 2018 Feb 17.
Hepatitis C virus (HCV) infection remains the main risk factor for chronic hepatitis (CHC), liver cirrhosis, and hepatocellular carcinoma (HCC). Changes in microRNA (miRNA) profiles can be associated with HCV infection and may either favor or inhibit the virus and/or its complication. Moreover, miRNAs have emerged as key regulators of various cancers including HCC. The aim of this work was to investigate the potentail role of miRNA-27a and miRNA-18b expression levels as non-invasive predictive biomarkers of hepatitis C virus-associated HCC. Furthermore, we aimed to explore potential association of these miRNAs expressions with HCC clinicopathological features' in Egyptian cases. This case control study included 200 participants [60 CHC patients, 39 post-HCV cirrhosis patients, 51 HCC cases], and 50 healthy volunteers. The serum miRNA-27a and miRNA-18b expression profiles were measured using quantitative real time-polymerase chain reaction (qRT-PCR). miRNA-27a and miRNA-18b expression levels were significantly increased in post-hepatitis C cirrhosis cases compared to control and CHC groups. In HCC group, only miRNA-27a expression levels were significantly increased. Moreover, miRNA-27a and miRNA-18b expression levels were positively correlated with distant metastasis, Child-Pugh grade, and lymph node metastasis. Logistic regression analysis revealed that miRNA-27a expression was an independent predictor of cirrhosis among CHC. Receiver operating characteristic (ROC) analyses showed that miRNA-27a and miRNA-18b expression levels were useful biomarkers discriminating cirrhosis from CHC (AUC were 0.672 and 0.487, respectively), and in differentiating HCC from post-hepatitis C cirrhosis (AUC were 0.897 and 0.723, respectively). By combined ROC analysis, power of miRNA-27a and miRNA-18b expression levels as discriminator between HCC from post-hepatitis C cirrhosis was high (AUC = 0.0.821). Serum microRNA-27a and miRNA-18b expression levels are promising diagnostic and non-invasive biomarkers of CHC, post-CHC cirrhosis, and HCC.
丙型肝炎病毒（HCV）感染仍然是慢性肝炎（CHC）、肝硬化和肝细胞癌（HCC）的主要危险因素。miRNA（miRNA）谱的变化可能与 HCV 感染有关，并且可能有利于或抑制病毒及其并发症。此外，miRNAs 已成为包括 HCC 在内的各种癌症的关键调节剂。本研究旨在探讨 miRNA-27a 和 miRNA-18b 表达水平作为丙型肝炎病毒相关 HCC 非侵入性预测生物标志物的潜在作用。此外，我们旨在探讨这些 miRNA 表达与埃及病例 HCC 临床病理特征的潜在关联。这项病例对照研究包括 200 名参与者[60 名 CHC 患者、39 名 HCV 后肝硬化患者、51 名 HCC 患者]和 50 名健康志愿者。使用实时定量聚合酶链反应（qRT-PCR）测量血清 miRNA-27a 和 miRNA-18b 表达谱。与对照组和 CHC 组相比，HCV 后肝硬化病例的 miRNA-27a 和 miRNA-18b 表达水平显著升高。在 HCC 组中，只有 miRNA-27a 的表达水平显著升高。此外，miRNA-27a 和 miRNA-18b 的表达水平与远处转移、Child-Pugh 分级和淋巴结转移呈正相关。逻辑回归分析显示，miRNA-27a 的表达是 CHC 肝硬化的独立预测因子。受试者工作特征（ROC）分析显示，miRNA-27a 和 miRNA-18b 的表达水平是区分肝硬化与 CHC 的有用生物标志物（AUC 分别为 0.672 和 0.487），也是区分 HCC 与 HCV 后肝硬化的有用生物标志物（AUC 分别为 0.897 和 0.723）。通过联合 ROC 分析，miRNA-27a 和 miRNA-18b 表达水平作为 HCC 与 HCV 后肝硬化鉴别指标的效能较高（AUC=0.821）。血清 microRNA-27a 和 miRNA-18b 表达水平是 CHC、HCV 后肝硬化和 HCC 的有前途的诊断和非侵入性生物标志物。
