Promoter region hypermethylation of cell cycle related gene in hepatocarcinogenesis

肝癌细胞周期相关基因启动子区高甲基化

• 批准号: 13670539
• 负责人: SASAKI Shigeru
• 金额: $ 2.3万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670539/
• 关键词: p16; cell cycle; suppressor gene; methylation; hepatocarcinogenesis; early diagnosis; risk factor for carcinogenesis; bio-marker for carcinogenesis; 発癌高危険群; 発癌予測マーカー; 肝癌; 発癌; 細胞周期制御遺伝子

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.

P16(Ink4a)抑癌基因因启动子区域高甲基化而失活，不仅在包括肝细胞癌在内的许多类型的肿瘤中被发现。我们先前的研究表明，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启动子区甲基化对肝癌发生的预测作用。在单因素分析中，p16蛋白缺失与肝癌的发生显著相关(p&lt；0.05)。在多因素分析中，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。我们的结果表明，p16蛋白表达缺失是肝癌发生的一个亚组的早期事件，它们的检测有助于对慢性肝炎患者进行随访，这些患者具有发展为肝细胞癌的高风险，例如有乙肝病毒或丙型肝炎病毒感染的患者。

项目成果

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Kaneto H.、Sasaki S.、Yamamoto H.、Itoh F.、Toyota M.、Suzuki H.、Ozeki I.、Iwata N.、Ohmura T.、Satoh T.、Karino Y.、satoh T.、Toyota J

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