流行病学资料显示幽门螺杆菌（H.pylori）东亚株流行的国家胃癌发病率远高于流行西方株的国家，H.pylori东亚株比西方株有更强的致癌性，但是机制并不清楚。我们推测西方株在传播到东亚国家后，其毒力因子CagA结构发生改变，赋予东亚株有更强的致癌性，以不完全同于西方株的致癌机制，引起东亚国家胃癌高发。本研究将从慢性萎缩性胃炎、消化性溃疡及胃癌标本中分离H.pylori东亚株，以西方株为对照，建立胃癌的动物模型，观察东亚株的致癌能力；将H.pylori东亚株感染胃癌细胞，用蛋白质组学技术，寻找东亚株感染细胞后的差异表达蛋白，探索胃癌高发的原因；构建含东亚型cagA或西方型cagA的表达载体，转染胃癌细胞，联用免疫共沉淀和蛋白质组学技术，研究东亚型CagA在胃癌细胞中的效应蛋白及其磷酸化修饰，并在胃癌组织中加以验证。揭示H.pylori东亚株引起胃癌高发的分子机制，阐明胃癌的发生发展。

The epidemiological investigation showed that the incidence of gastric cancer in countries with prevalence of East-Asia Helicobacter pylori (H .pylori) strains was even higher than that in countries with prevalence of Western H.pylori strains, and East-Asia H. pylori had stronger carcinogenicity than Western type. But the pathogenic mechanism was unclear. We hypothesized that the structure of the virulence factor CagA was changed after transmission of Western H. pylori to East-Aisa region, which endowed East-Asia H. pylori with stronger carcinogenicity, resulting in high incidence of gastric carcinoma in East Asian countries as the different mechanism from Western type. In the study, East-Asia H. pylori strains are isolated from gastric biopsy specimens from the patients with chronic atrophic gastritis, peptic ulcer and gastric cancer. The animal models are established by H. pylori isolates and their oncogenic potential is observed. Then human gastric cancer cell line AGS cells are infected with the isolates and control Western strains, and the differently expressed proteins are obtained by two-dimensional electrophoresis (2-DE) and identified by LC-MS/MS to explore the cause of high incidence of gastric carcinoma. Further, the eukaryotic expression vector, carrying the full-length East-Asia cagA or Western cagA gene, are constructed and used to transfect AGS cells to study the effector proteins binding to East-Asia CagA and their phosphorylation modification by the co-immunoprecipitation and proteomics technology. Finally, the differential proteins and effector proteins are verified in gastric cancer tissues. Our results shall reveal the molecular mechanism of East-Asia H. pylori leading to high incidence of gastric carcinoma and elucidate the development and progression of gastric cancer.