Promoter region hypermethylation of cell cycle related gene in hepatocarcinogenesis

启动子区超甲基化导致p16 （INK4A）肿瘤抑制基因失活，不仅在许多类型的肿瘤中都有发现，包括肝细胞癌（HCC）。我们之前的研究表明，p16启动子区域的甲基化和由此导致的p16蛋白表达缺失是肝癌发生的一个亚群的早期事件。本研究的目的是确定p16蛋白表达缺失和p16启动子区域甲基化作为肝癌发生的预后因素的有效性。在单因素分析中，p16蛋白的缺失与肝癌发生显著相关（p<0.05）。在多变量分析中，性别、年龄、纤维化和p16蛋白表达缺失仍具有独立的预后意义。我们的研究结果表明，p16蛋白表达的缺失是肝癌发生的一个亚群的早期事件，它们的检测对于随访发生HCC的高风险慢性肝炎患者（如HBV或HCV感染患者）是有用的。

Inactivation of the p16 (INK4A) tumor suppressor gene by promoter region hypermethylation has been shown not only in many types of tumor, including hepatocellular carcinoma (HCC). Our previous study suggested that methylation of the p16 promoter region and the resulting loss of p16 protein expression are early events in a subset of hepatocarcinogenesis.The objective of this study was to determine the usefulness of the loss of p16 protein expression and the methylation of the p16 promoter region as a prognostic factor for hepatocarcinogenesis.In univariate analysis, loss of p16 protein was significantly correlated with hepatocarcinogenesis (p<0.05). In multivariate analysis, sex, age, fibrosis and loss of p16 protein expression retained independent prognostic significance.Our results suggest that the loss of p16 protein expression are early events in a subset of hepatocarcinogenesis and that their detection is useful to follow up chronic hepatitis patients with a high risk for developing HCC, such as those with HBV or HCV infections.