幽门螺杆菌(Hp)cagA基因与胃癌发生发展密切相关，但其机制不明。本课题组应用Hp与胃癌细胞共培养模型，发现Hp cagA基因阳性与肿瘤相关蛋白α-烯醇酶(ENO1)高表达有关，并于2014年首次报道CagA蛋白调控ENO1表达的信号通路。但CagA对ENO1表达的调控作用尚未在人或动物体内证实。因此，提出假说：CagA蛋白在体内通过调控ENO1表达促进胃癌发生。项目同时采用Hp cagA阳性菌株和基因敲除菌株构建Hp感染沙鼠动物模型，在从Hp感染至胃癌发生期间，定期检测胃上皮细胞ENO1 mRNA表达水平，并对胃部病变进行病理学分级量化，经logistic回归分析，探讨ENO1表达与CagA及胃部癌变进程的关系；并用临床标本的检测结果印证动物实验结论；结合本研究发现与现有证据，证实假说。项目有望对Hp感染致癌机制研究产生重大影响，并为胃癌的早期诊断和预防提供关键性理论依据。

Helicobacter pylori cagA gene is closely associated with development and progression of gastric cancer, but the involved mechanism still remains undefined. This research group previously observed that the cagA gene was related to the overexpression of α-enolase (ENO1) by using a co-culture model of H. pylori and gastric carcinoma cells, and made the first report in 2014 on identification of a cellular signal pathway for the CagA regulation of ENO1 expression. Nevertheless, it has not been evidenced that CagA regulates the expression of ENO1 in human and animals. Thus, we propose the hypothesis that in vivo CagA might promote gastric carcinogenesis by regulating ENO1 expression. This project is formulated to establish gerbil models of H. pylori infection using cagA positive and knockout strains, respectively, measure mRNA expression levels of ENO1 in the gastric epithelial cells, perform pathologic grading of gastric lesions at regular intervals during the process from gastric infection to cancer, and carry out logistic regression analysis of the data, with the aim to ascertain the associations of the ENO1 expression with CagA as well as the progress of gastric canceration. The conclusion of the animal experiments will be confirmed with the data from examination of clinical gastric specimens, and basing on the findings of this study together with the present data, the hypothesis will be demonstrated. This study is hopeful to impact significantly the researches on H. pylori-involved carcinogenic mechanisms, and provide the crucial theory basis for early diagnosis and prevention of stomach cancer.