死亡相关蛋白激酶基因高甲基化在胃癌形成过程中作用的初步研究

Preliminary Study on Role of Hypermethylation of Death-associated Protein Kinase Gene in the Development of Gastric Cancer

背景:DNA启动子区甲基化可导致肿瘤抑制基因表达沉默,在胃癌的发生、发展中发挥重要作用。目的:观察正常胃黏膜、慢性萎缩性胃炎伴肠化生、异型增生和早期胃癌组织中死亡相关蛋白激酶(DAPK)基因启动子区甲基化状态,探讨其与胃癌发生、发展的关系。方法:以甲基化特异性聚合酶链反应(MSP)检测20例正常胃黏膜、14例慢性萎缩性胃炎伴肠化生、27例异型增生和16例早期胃癌组织中DAPK基因启动子区甲基化状态,并分析其与患者临床病理特征的关系。结果:早期胃癌组织中DAPK基因启动子区甲基化率显著高于正常胃黏膜、慢性萎缩性胃炎伴肠化生和异型增生组织(43.8%对0%、7.1%和11.1%,P<0.05),而后三者之间DAPK基因启动子区甲基化率无明显差异。DAPK基因启动子区甲基化与患者性别、年龄和病变部位均无关,与幽门螺杆菌(H.pylori)感染和血清癌胚抗原(CEA)水平显著相关(P<0.05)。结论:DAPK基因启动子区高甲基化是胃癌发生的早期分子事件,在由慢性萎缩性胃炎伴肠化生和异型增生进展至早期胃癌的过程中起重要作用。

Background： Methylation of DNA promoter region can cause silencing of tumor suppressor gene, and plays an important role in the development and progression of gastric cancer. Aims： To investigate hypermethylation of deathassociated protein kinase （DAPK） gene promoter region in tissues of normal gastric mucosa （NGM）, chronic atrophic gastritis with intestinal metaplasia （IM）, dysplasia （DYS） and early gastric cancer （EGC）, and to appraise its relationship with the development and progression of gastric cancer. Methods： Methylation of DAPK gene promoter region was determined by methylation-specific polymerase chain reaction （MSP） in tissues of 20 NGM, 14 IM, 27 DYS and 16 EGC, and its relationship with patients＇ clinicopathological characteristics was analyzed. Results： The methylation rate of DAPK gene promoter region in tissue of EGC was significantly higher than that in tissues of NGM, IM and DYS （43.8% vs. 0%, 7.1% and 11.1%, respectively, P〈0.05）. No significant difference was found between NGM, IM and DYS. Hypermethylation of DAPK gene promoter region was significantly correlated with Helicobacter pylori （H. pylori） infection and the level of serum carcinoembryonic antigen （CEA） （P〈0.05）, but not with gender, age and location of lesions. Conclusions： Hpermethylation of DAPK gene promoter region is an early event in the tumorigenesis of gastric cancer and plays an important role in the progression of chronic atrophic gastritis with IM and DYS to EGC.