PDF(Pubmed)
Abstract：
Risk factors for hepatocarcinogenesis include chronic inflammation due to viral infection, liver fibrosis, and aging. In this study, we separated carcinogenic and non-carcinogenic cases due to hepatitis C virus (HCV) infection, aiming to comprehensively analyze miRNA expression in liver tissues by age, and identify factors that contribute to carcinogenesis. Total RNA was extracted from 360 chronic hepatitis C (CH), 43 HCV infected hepatocellular carcinoma (HCC), and surrounding non-tumor (SNT) tissues. MicroRNA (miRNA) expression patterns were analyzed using microarray. Using machine learning, we extracted characteristic miRNA expression patterns for each disease and age. There were no age-dependent changes in miRNA expression in the disease-specific comparisons; however, miRNA expression differed among the age groups of 50, 60, and 70 years of age between CH and SNT. The expression of miRNA was different between SNT and HCC only in patients in their 70s. Of the 55 miRNAs with significant differences in expression between CH and SNT, 34 miRNAs showed significant differences in expression even in the degree of liver fibrosis. The observation that miRNAs involved in hepatocarcinogenesis differ at different ages suggests that the mechanisms of carcinogenesis differ by age group as well. We also found that many miRNAs whose expression did not affect liver fibrosis were involved in carcinogenesis. These findings are expected to define biomarkers for detection of HCC at early stage, and develop novel therapeutic targets for HCC.
摘要：
肝癌发生的危险因素包括病毒感染引起的慢性炎症，肝纤维化,和衰老。在这项研究中,我们分离了由丙型肝炎病毒（HCV）感染引起的致癌和非致癌病例，旨在按年龄综合分析肝脏组织中miRNA的表达，并确定导致癌症发生的因素。从360例慢性丙型肝炎（CH）中提取总RNA，43HCV感染的肝细胞癌（HCC），和周围的非肿瘤(SNT)组织。使用微阵列分析微小RNA(miRNA)表达模式。使用机器学习，我们提取了每种疾病和年龄的特征性miRNA表达模式。在疾病特异性比较中，miRNA表达没有年龄依赖性变化；然而，在CH和SNT之间的50、60和70岁年龄组中，miRNA的表达有所不同。仅在70多岁的患者中，SNT和HCC之间的miRNA表达有所不同。在55个在CH和SNT之间表达差异显著的miRNAs中,34个miRNAs即使在肝纤维化程度上也显示出显著的表达差别。参与肝癌发生的miRNA在不同年龄的观察结果不同，这表明癌症发生的机制也因年龄组而异。我们还发现许多表达不影响肝纤维化的miRNA参与了癌变。这些发现有望为早期HCC的检测定义生物标志物，并开发新的肝癌治疗靶点。
