中文摘要：

目的通过检测胃癌癌旁距离原发灶不同距离组织及胃癌原发灶RASSF1A基因启动子区甲基化状态的差异,分析正常胃组织、癌前病变及癌组织中该基因甲基化的动态变化以及RASSF1A基因甲基化与胃癌原发灶病理生物学行为的关系,探讨RASSF1A基因启动子区甲基化在胃癌阶段性发生及进展中的作用及临床意义。方法采用甲基化特异性PCR（MSP）法检测距胃癌癌灶边缘5、3、1cm组织及胃癌原发灶组织中RASSF1A基因甲基化状态。结果 RASSF1A基因启动子区甲基化发生率在距胃癌灶边缘5、3、1cm组织及胃癌组织中分别为5.0%、7.5%、22.5%及42.5%,从距癌灶边缘5cm胃组织至胃癌原发灶组织中的表达中随距癌灶边缘距离的减少呈上升趋势,差异有统计学意义（P〈0.01）。从组织病理学角度分析,RASSF1A基因启动子区甲基化发生率在正常胃组织、癌前病变组织及胃癌原发灶中分别为0.0%、17.39%、42.5%,动态上升,三者间差异具有统计学意义（P〈0.01）。RASSF1A基因甲基化发生率在胃癌患者透浆膜组显著高于未透浆膜组（P〈0.05）;在转移淋巴结数7枚以上组显著高于0～7枚组（P〈0.05）,与胃癌胃壁浸润深度、转移淋巴结数相关,在不同大体类型、生长方式、分化程度、性别及年龄胃癌患者间差异无统计学意义（P〉0.05）。结论 RASSF1A基因启动子区异常甲基化可能与胃癌的阶段性发生及临床进展相关。

英文摘要：

Objective To investigate hypermethylation of RASSF1A gene in stage carcinogenesis and progression of human gastric cancer and its clinical significance through detecting the difference of promoter hypermethylation of RASSF1A gene in gastric cancer tissues and the paracarcinoma tissues,and analyzing the dynamic change of hypermethylation of RASSF1A gene from paracarcinoma normal gastric tissues, precancerosis tissues：othe cancer site,as well as studying the relationship of hypermethylation of RASSF1A gene and clinico-pathological features of gastric cancer. Methods Forty patients with primary human gastric cancers were involved in this study. The methylation state of RASSF1A gene was detected by methylation-specific PCR（MSP）. Results Promotor hypermethylation of RASSF1A gene in the co-responding 5,3, lcm paracarcinoma tissues and gastric cancer tissues was 5 %, 7.5 %, 22.5 % and 42.5 % respectively, which exhibited a upgrading tendency with the decrease of distance from 5cm paracarcinoma tissues to the cancer sites,and the difference among them was significant（P〈0.01）. Analyzed histopathologically,hyperm- ethylation of RASSF1A gene of paracarcinoma normal gastric tissues, precancerosis tissues and the cancer site itself was 0%, 17.4 %, and 42.5 % respectively, which increased dynamicly, and the difference was significant among the three groups（P〈0.01）. Hypermethylation of RASSF1A was related to the penetration depth of gastric walls and also the number of lymphatic node metastasis of gastric cancer. No statistical difference of hypermethylation of RASSF1A gene was found between different gross types, growth patterns,differentiation degrees, ages and sex of gastric cancer （P 〈 0. 05）. Conclusion Promotor hypermethylation of RASSF1A gene is related to stage carcinogenesis and progression of human gastric cancer.