HCC患者GSTP1基因启动子区CpG岛甲基化状态研究

Detection of Aberrant Promoter CpG Islands Hypermethylation of GSTP1 in Human Primary Hepatocellular Carcinomas

目的检测人原发性肝癌(HCC)中抑癌基因GSTP1的启动子区CpG岛甲基化的状况,并探讨其在肝癌发生中的作用。方法以已知的GSTP1基因启动子区CpG岛甲基化阳性的乳腺癌细胞株MCF-7为阳性对照,以11例正常人外周血单核细胞(PBMC)DNA为阴性对照,用甲基化特异性PCR(MSP)的方法对26例肝细胞癌患者的癌、远癌组织中GSTP1基因启动子区CpG岛甲基化的状态进行检测。结果在26例原发性肝癌中GSTP1基因启动子区CpG岛甲基化在癌组织为88%(23/26),在远癌组织中为69%(18/26);而在11例正常人外周血单核细胞均为甲基化阴性。结论抑癌基因GSTP1基因启动子区CpG岛高甲基化可能是肝癌发生早期的分子事件,在人原发性肝癌的发生发展中具有重要的作用。

Objective To detect the aberrant promoter CpG islands hypermethylation status of GSTP1 gene in hepatocellular carcinomas（HCC） and to assess its significant role in hepatocarcinogenesis. Methods Surgically resected cancerous and non-cancerous liver tissues of 26 hepatocellular carcinoma patients were obtained from West China Hospital, and 11 peripheral blood samples from healthy donors as negative control were collected. Breast cancer cell line MCF-7 with CpG islands hypermethylation of GSTP1 as positive control was obtained from the Cell Bank of Chinese Academy of Sciences in Shanghai. All genomic DNA were extracted using common phenolchloroform approach, and the 5＇ CpG islands methylation status of GSTP1 gene was studied by methylation-specific polymerase chain reaction （MSP）. Results GSTP1 gene promoter CpG island hyperthylation was detected in 88. 5%（23/26） of cancerous tissues and in 69% （18/26） of corresponding non-cancerous tissues from the 26 HCC patients. None of the 11 control samples were methylation positive. Conclusion The data indicates that the detection of GSTP1 gene methyl-lation may be a valuable biomarker by MSP for HCC early diagnosis and disease monitoring.