胃液脱落细胞DNA甲基化在胃癌中的生物学意义

目的:探索在胃癌患者胃液脱落细胞中检测肿瘤相关基因启动子区DNA甲基化的可行性,及其与临床病理之间的关系。方法:采用MSP(甲基化特异性PCR)方法,对117例胃癌及165例非胃癌患者胃液脱落细胞P16、DAPK(死亡相关蛋白激酶)、E-cadherin(上皮细胞钙黏蛋白)、hMLH1(错配修复基因)四种基因启动子区甲基化状态进行检测;并与组织、血浆检测结果进行比较。结果:不同标本四种基因异常甲基化的频率,胃癌组明显高于对照组,差异有统计学意义(P<0.001)。P16、E-cadherin、DAPK发生甲基化的频率,早期胃癌与进展期胃癌相比,差异无统计学意义(P>0.05)。胃癌组胃液脱落细胞各基因甲基化状态与患者年龄、性别、肿瘤大小、H.pylori感染无关。结论:通过胃液脱落细胞检测肿瘤相关基因DNA甲基化有望作为检测胃癌的生物学标志物。

The Biological Significance of Detecting DNA Promoter Hypermethylation by Exfoliated Cells of Gastric Juice in Gastric Cancer

Objective:To explore the feasibility of detecting DNA hypennethylation of tumor related genes and analyze the relationship between DNA hypennethylation and biological significance in patients with gastric cancer.Methods:We examined the methylation status of multiple genes in gastric juice by Methylaion-Specific PCR(PCR).And also determined the promoter methylation frequencies of 4 tumor related genes,including P16、E-cadherin、DAPkinase、hMLH1,including gastric cancer(n=117) with control group(n=165),then we compared the results with tissues and plasma.Results:In gastric cancer group,methylation frequencies were significantly higher than the control group(P<0.0l);There was no significance of promoter methylation frequencies of both P16、E-cadherin and DAPKinase between EGC(Early gastric cancer) with AGC(Advanced gastric cancer)(P>0.05).There was no significant relation between hypennethylation of the four candidate genes and age,gender,tumor size、H.pylori infection in patients with gastric cancer,while hypennethylation of P16 and hMLHl correlate with lymph nodes metastasis(with P value 0.04 and 0.02,respectively ).Additionally,in the control group,the average age was older in patients with aberrant DNA hypermethylation(P value<0.05).Conclusion:Our data suggested that detecting DNA promoter methylation of multiple genes by exfoliated cells of gastric juice may be a potential biomarker for diagnosis of gastric cancer.