摘要
目的检测临床手术切除43例胃癌及相应正常组织COX-2、hMLH1和hMSH2微卫星不稳定状态MSI及三种基因启动子甲基化情况,并进一步探讨它们与胃癌发生的关系。方法采用聚合酶链反应(PCR)技术检测5个位点的MSI状态;甲基化特异性PCR(Methylation specific PCR,MSP)方法检测胃癌及正常组织COX-2、hMLH1及hMSH2三种基因启动子CpG岛甲基化状态。结果43例胃癌中MSI总检出率为48.84%(21/43),五个位点的MSI检出率无显著差别。COX-2和hMLH1基因启动子CpG岛甲基化在43例胃癌中分别有8例和13例,正常组织中未检测到。hMSH2基因启动子CpG岛在胃癌及正常组织中均未检测到甲基化。在MSI-H组hMLH1基因启动子CpG岛甲基化率显著高于MSS组(P<0.01);而在MSI-H和MSI-L组间以及MSI-L和MSS无差别。MSI-H组中COX-2基因启动子CpG岛甲基化8例,且有7例胃癌同时出现hMLH1和COX-2基因启动子CpG岛甲基化。结论在MSI胃癌(尤其是MSI-H型胃癌)的发生、发展过程中可能同时出现了hMLH1和COX-2基因启动子CpG岛的甲基化(即表型遗传修饰)。MSI胃癌hMLH1基因启动子CpG岛甲基化率高于MSS胃癌,提示检测hMLH1基因启动子CpG岛甲基化对于判断肿瘤类型有一定意义。
Objective To investigate the COX-2, hMLH1 and hMSH2 of genes promoter methylation and MSI frequency in 43 cases of human gastric carcinoma and normal tissues, and to evaluate the relationship between them and occurrence of gastric carcinoma. Methods Methylation specific PCR （MSP） and polymerase chain reaction （PCR） methods were employed in this study in order to investigate the promoter methylation of these genes and 5 loci MSI frequency in human gastric carcinoma and normal tissues. Results Of 43 gastric carcinoma cases, the total frequency of MSI was 48.84% （21/43）. The MSI frequency no significant discrepancy was found among the 5 loci. Cases with methylation of COX-2 and hMLH1 gene promoter CpG islands in gastric carcinoma were 8 and 13, and they were not detected in normal tissues. Methylation of hMSH2 gene promoter CpG islands was not detected in gastric carcinoma or normal tissues. The methylation rate of hMLH1 gene promoter CpG islands in MSI-H was higher than that in MSS （P〈0. 01）. There was no significant difference between MSI-H and MSI-L, and the same result was found between MSI-L and MSS. 8 cases with methylation of COX-2 gene promoter CpG islands only occurred in MSI-H gastric cancer, and 7 cases both with methylation of COX-2 and hMLH1 gene pro- moter CpG islands was observed in MSI-H. Conclusion Methylation of hMLH1 and COX-2 gene promoter CpG islands may both occur in the development of MSI gastric carcinoma. The methylation rate of hMLH1 gene promoter CpG islands in MSI gastric carcinoma was higher than that in MSS gastric carcinorma. It suggested that detecting the methylation of hMLH1 gene promoter CpG islands might be a useful method for determining the gastric carcinoma type.
出处
《肿瘤防治研究》
CAS
CSCD
北大核心
2007年第3期171-174,共4页
Cancer Research on Prevention and Treatment
基金
河北省自然科学基金资助项目(303485)
