肝细胞癌组织中RAS相关区域家族蛋白1A、肿瘤高甲基化基因1和P73基因的异常甲基化  

Hypermethylation of Ras association domain family protein 1A,hypermethylated in cancer 1 and p73 genes in hepatocellular carcinoma

作　　者：赵中海[1] 耿小平[1] 朱立新[1] 李晓明[2] 刘宗石[2] 

机构地区：[1]安徽医科大学第一附属医院肝胆外科,合肥230022 [2]香港中文大学医学院病理解剖及细胞学系

出　　处：《中华外科杂志》2005年第23期1528-1532,共5页Chinese Journal of Surgery

基　　金：安徽省自然科学基金资助项目(03043702);香港政府大学研究拨款委员会基金资助项目[RGC;IDCUHK4066/02M(2140319)]

摘　　要：目的探讨肝细胞癌中RAS相关区域家族蛋白1A(RASSF1A)、肿瘤高甲基化基因1(H IC1)和P73基因启动子异常甲基化状况及其与患者临床和病理因素之间的关系。方法收集肝细胞癌组织标本和对应的远癌组织标本各40例及2例健康人的肝组织标本;通过甲基化特异的聚合酶链反应方法检测这些标本中RASSF1A、H IC1和P73基因启动子区的甲基化状况。结果RASSF1A基因在癌和远癌组织中启动子区的甲基化率分别为90.0%和72.5%,癌组织中的甲基化率高于远癌组织(P<0.05)。H IC1基因在癌和远癌组织中的甲基化率分别为77.5%和70.0%。P73基因在癌组织中甲基化率为5.0%,在远癌组织没有发现甲基化。健康人肝组织中未发现任何上述基因的异常甲基化。远癌组织中H IC1基因甲基化患者的年龄[(48±14)岁]比无甲基化患者[(57±11)岁]小(T=2.049,P=0.047)。3个基因甲基化发生情况与患者性别、是否合并乙型肝炎、肝硬化、甲胎蛋白水平、肿瘤大小、有无包膜和门静脉癌栓以及TNM分期之间未发现有统计学相关性。结论肝细胞癌中RASSF1A和H IC1基因启动子的高甲基化是普遍现象,年轻肝细胞癌患者H IC1甲基化现象更常见。Objective To evaluate the status of promoter hypermethylation of Ras association domain family protein 1 A（ RASSF1 A）, hypermethylated in cancer 1 （ HIC1 ） and p73 genes in hepatocellular carcinoma （HCC） and to explore the correlation with clinicopathological features. Methods Forty cases of HCC and their corresponding non-tumor liver tissues, other 2 cases of healthy donor livers were detected using methylation specific polymophorisim chain reaction （MSP） method. Results The frequency of promoter hypermethylation of RASSF1A showed 90. 0% and 72.5% in tumor and corresponding non-tumor tissues respectively, and there was significant difference between them （P 〈 0. 05 ）. The frequency of promoter hypermethylation of HIC1 showed 77. 5% and 70. 0% in tumor and corresponding non-tumor tissues respectively. The frequency of hypermethylation of HIC1 in non-tumor liver tissues showed significant correlation between younger and older patients. The frequency of promoter hypermethylation of p73 showed 5.0% in tumor tissues. However, none of hypermethylation of the gene was detected in corresponding non- tumor liver tissues. There was none of hypermethylation of the three genes showed in two cases of healthy donor livers. Conclusion Promoter hypermethylation of RASSF1A and HIC1 genes are common event in HCC and play an important role in the pathogenesis and may be used to develop novel diagnostic andtherapeutic approaches for HCC in the future.

关 键 词：肝细胞癌 DNA甲基化 基因 肿瘤抑制 

分 类 号：R735.7[医药卫生—肿瘤] R730.2[医药卫生—临床医学]