人胎盘型谷胱甘肽S转移酶在胃癌组织中的表达与基因甲基化关系的研究

Expression of GST- and Methylation of GST- DNA in Human Gastric Cancer

目的：研究胃癌组织中ＧＳＴ－π的表达与其基因甲基化状态的关系。方法：应用Ｓ－Ｐ法检测１１６例胃癌和５３例胃癌前病变的ＧＳＴ－π表达和限制性内切酶及ＰＣＲ、Ｓｏｕｔｈｅｒｎ印迹方法检测１４例胃癌及其相应正常胃粘膜ＧＳＴ－πＤＮＡ５′端调控区ＣＣＧＧ特定位点的甲基化水平。结果：ＧＳＴ－π阳性率，正常胃粘膜１０％（４／３９），胃癌７７％（８９／１１６），肠上皮化生７６％（１９／２５），不典型增生８９％（２５／２８）。ＧＳＴ－π在胃癌及癌前病变中的表达较正常胃粘膜增高（Ｐ＜００１）。胃癌组织中ＧＳＴ－π基因较正常胃粘膜呈现高度去甲基化（Ｐ＜００１），胃癌ＧＳＴ－π基因５′端调控区低甲基化与其ＧＳＴ－π表达增加呈相关性（Ｐ＜００５）。结论：ＧＳＴ－π在胃癌及癌前病变中的表达与胃癌的发生发展密切相关，ＧＳＴ－π可作为胃癌的肿瘤相关抗原；ＧＳＴ－π基因５′端调控区低甲基化可能是ＧＳＴ－π高表达的分子机理。

Objective: To study the relationship between the expression of GST- and methylation status of GST- gene in gastric cancers Methods: The GST- was detected in 116 human gastric cancers and 53 precancerous lesions with S-P immunohistochemical method using GST- monoclonal antibody The methylation status of the 5end regulatory sequence CCGG site of GST- gene was also investigated by means of restriction endonuclease analysis, PCR and Southern blotting methods in 14 human gastric cancers and normal gastric mucosa Results: The positive rate of GST- in normal gastric mucosa, intestinal metaplasia, atypical hyperplasia and gastric cancer were 10%(4/39), 76%(19/25), 89%(25/28), 77%(89/116) respectively The positive rate in gastric cancer and precancerous lesions were markedly higher than that of the normal gastric mucosa (P< 001) As compared with that of the normal gastric mucosa, the GST- DNA of gastric cancer was markedly hypomethylated (P< 001) A close correlation existed between overexpression of GST- DNA methylationand hypomethylation of GST- DNA in gastric cancer (P< 005) Conclusion: GST- is probably involved in the carcinogenesis and development of gastric cancer, and is a tumor associated antigen of gastric cancer Hypomethylation of GST- gene might be a molecular factor responsible for overexpression of GST-