hMLH1基因甲基化在胃癌早期诊断中的应用价值  

Implication of hMLH1 gene methylation in early diagnosis of gastric carcinoma

作　　者：易默[1] 周健[1] 李颖[1] 史丽萍[1] 何小勤[1] 

机构地区：[1]陕西省人民医院消化内二科,西安710068

出　　处：《国际消化病杂志》2016年第5期299-302,共4页International Journal of Digestive Diseases

基　　金：陕西省科技厅社会发展攻关项目(2013k12-03-18)

摘　　要：目的探讨hMLH1基因表达和甲基化与胃癌的关系,旨在为胃癌早期诊断治疗提供新思路。方法选取本院2013年5月至2015年7月收治的肠上皮化生34例、异型增生37例、胃癌41例,胃镜活组织检查收集病理组织,另选取同期医院门诊收集的30例正常胃黏膜组织作为对照组。通过甲基化特异聚合酶链反应和免疫组织化学方法检测hMLH1基因表达和甲基化水平,并进行组间对比分析。结果 hMLH1基因甲基化率依次为肠上皮化生组20.6%,异型增生组43.2%,胃癌组51.2%,对照组3.3%;与对照组相比较,肠上皮化生组hMLH1基因甲基化水平有所升高但差异无统计学意义(P>0.05),异型增生组和胃癌组均显著升高,差异具有统计学意义(P均<0.01),且异型增生组及胃癌组甲基化水平均显著高于肠上皮化生组(P均<0.05)。组织样本中hMLH1基因蛋白表达阳性率分别为肠上皮化生组73.5%,异型增生组54.1%,胃癌组31.7%,对照组100%;与对照组相比较,肠上皮化生组、异型增生组及胃癌组hMLH1基因蛋白表达阳性率均显著降低,且差异有统计学意义(P均<0.01)。hMLH1基因蛋白表达水平与基因甲基化水平呈负相关(r=-0.4675,P<0.01)。结论 hMLH1基因启动子区高甲基化可通过调节hMLH1蛋白表达在胃癌发生发展中起作用。Objective This paper investigated the relationship between hMLH1 genemethylation and protein expressionand gastric carcinoma in order to provide a new method for early diagnosis of gastric carcinoma. Methods A total of 142 tissue samples （including 34 cases of intestinal metaplasia, 37 cases of dysplasia, 41 cases of gastric carcinoma and 30 cases of normal） were selected for detecting DNA methylation and protein expression status using methylation specific PCR and immunohistochemical staining from May in 2013 to July in 2015 and the differences among groups were compared. Results The positive rate of DNA methylation rate is 20.6% in intestinal metaplasia, 43.2% in dysplasia, 51.2% in gastric cancer, and 3.3% in the control group. There is no significant difference in positive rate of DNA rnethylation rate between intestinal metaplasia and the control （P〉0.05）, but compared with the control group, there is significant difference between higherin dysplasia and gastric cancer （P〈 0. 01）; and compared with intestinal metaplasia, there is significant difference between higherin dysplasia and gastric cancer （P〈0. 05）. The positive rate of hMLH1 protein is 73. 5% in intestinal metaplasia, 54.1% in dysplasia, 31.7% in gastric cancer, and 100% in the control group. All those tissues have significant difference compared to the control group （P〈0.01）. A significantly negative relationship exists between the methylation level and the protein expression level in hMLH1 （r= - 0. 4675, P〈0.01）. Conclusion The DNA methylation which occurred in promoter regions of hMLHI genes depresses the protein expression, and may participate in the occurrence and progression of gastric cancer.

关 键 词：HMLH1基因 甲基化 胃癌 诊断 

分 类 号：R735.2[医药卫生—肿瘤]