肝细胞癌ASC基因启动子区甲基化及其mRNA表达研究  

Promoter Methylation and mRNA Expression of ASC Gene in Hepatocellular Carcinoma

作　　者：白彧[1] 杜智[1] 高英堂[1] 杨斌[1] 朱争艳[1] 李雅玥[1] 王毅军[1] 刘彤[1] 

机构地区：[1]天津医科大学第三中心医院肝胆外科,天津市人工细胞重点实验室,天津市300170

出　　处：《中国肿瘤临床》2011年第8期437-441,共5页Chinese Journal of Clinical Oncology

基　　金：天津市重点科技攻关专项资金(编号:05YFSZSF02500);天津市科委科技攻关计划面上项目(编号:08JCYBJC08300)资助~~

摘　　要：目的:探讨肝细胞肝癌(HCC)ASC基因启动子区甲基化与mRNA表达及其临床病理特征的关系。方法:运用甲基化特异性聚合酶链反应(MSP)和实时荧光定量PCR技术,检测58例肝细胞癌及其相应癌旁组织、15例肝硬化肝组织、5例慢性病毒性肝炎肝组织和5例正常肝组织中ASC基因启动子区甲基化状态及其mRNA的表达水平。结果:58例肝细胞癌组织中有40例(69.0%)发生ASC基因启动子区甲基化,其相应癌旁组织中有27例(46.6%)发生该基因启动子区甲基化,而在肝硬化、肝炎和正常肝组织中均未检测到该基因启动子区甲基化。ASC基因在肝细胞癌组织中甲基化频率高于其相应癌旁组织(P=0.015)。ASC基因启动子区甲基化与肿瘤直径(P=0.001)、生长方式(P=0.003)以及国际抗癌联盟第6版TNM(TNM6)分期(P=0.001)有关。以ASC基因在正常肝组织中的表达量为参照,58例肝细胞癌组织中有33例出现ASC基因mRNA低表达或表达缺失,其相应癌旁组织中有14例出现低表达或表达缺失,而在肝硬化及肝炎肝组织中ASC基因mRNA均呈正常表达。与癌旁组织相比,肝细胞癌组织中ASC基因mRNA表达明显下调(P<0.05)。在发生ASC基因启动子区甲基化的40例肝细胞癌组织中有26例出现mRNA低表达。结论:ASC基因启动子区甲基化是肝细胞癌中的频发事件,可能在肝细胞癌的进展中起重要作用。Objective： To investigate the promoter methylation and mRNA expression of ASC gene and its clinicopathological significance in hepatocellular carcinoma （ HCC ）. Methods： Methylation specific PCR was employed to detect the methylation status of ASC gone promoter in 58 HCC and their matched adjacent noncancerous tissue samples, 15 liver cirrhosis, 5 chronic viral hepatitis and 5 nonzqal liver samples. Real-time fluorescent quantitation PCR was performed to examine the expression ofASC mRNA. Results： Aberrant methylation of the ASC gene was detected in 40 of 58 （ 69.0% ） HCC tissues, and 27 of 58 （ 46.6% ） corresponding noncancerous tissues. There was no methylation found in liver cirrhosis, chronic viral hepatitis and normal liver samples. The frequency of methylation of ASC gene promoter was higher in HCC than in adjacent noncancerous tissue （ P = 0.015 ）. ASC gene methylation was significantly associated with tumor size （ P = 0.001 ）, growth pattern （ P = 0.003 ） and TNM staging （UICC 6th edition） （ P = 0.001 ）. Compared with those in normal liver tissue, mRNA levels were downregulated in 33 cancerous and 14 noncancerous tissue samples. ASC mRNA level was significantly lower in HCC tissue than in adjacent noncancerous tissue （ P 〈 0.05 ）. In 40 HCC tissue samples with ASC methylation, 26 showed low level of mRNA expression. Conclusion： The hypermethylation of ASC gene promoter is frequent and may play an important role in the development of HCC.

关 键 词：肝细胞癌 ASC基因 甲基化 实时荧光定量PCR 

分 类 号：R735.7[医药卫生—肿瘤]