胃癌是复杂的多基因疾病，其癌变是一个渐进的多步骤、多阶段过程。胃癌进展的疾病模型包括了幽门螺杆菌感染、慢性萎缩性胃炎、肠上皮化生、不典型增生、胃癌等阶段。MST信号通路是进化上高度保守的能够调控细胞的增殖、分化、凋亡，进而调控组织稳定和器官生长的通路。这条通路由13个核心成员构成了一个激酶级联反应，其是一肿瘤抑制通路，成员的功能异常和癌症的发生发展相关。研究显示这一通路的许多成员参与了胃癌的发生发展。本项目将用病例-对照关联研究的方法，采用全面广泛的标记单核苷酸多态性（Tag-SNPs）途径检测MST1和MST2基因多态性与幽门螺杆菌感染、胃癌发生的关系，确定MST1和MST2在正常组织和胃癌变组织中的蛋白表达差异，并初步探讨易感多态性与蛋白表达水平的关系，为胃癌预防措施的制订和精准医疗、基因治疗、开发新药提供理论和实验依据。

It is well accepted that gastric cancer is a complex polygenetic disease. It is the result of a long complex multifactorial and multistep process that involves well-characterized sequential stages. The pathological model of stomach cancer progression includes Helicobacter pylori (H. pylori) infection, atrophic gastritis, intestinal metaplasia, dysplasia, and gastric cancer. The MST pathway is a highly evolutionary conserved pathway, whose main physiological function is to control cell proliferation, differentiation, apoptosis, and hence tissue homeostasis and organ growth. The core signaling consists of 13 members, which forms a kinase cascade. MST pathway is reported to be a tumor-suppressive signal pathway, and functional dysregulation of its core components is always associated with the development of cancer. Some studies indicate that many members in MST pathway may be involved in the initiation and progression of gastric cancer. We will explore the relationships between the polymorphisms in MST1 and MST2 genes and H. pylori infection, as well as gastric cancer risk, using a tagging SNP approach in a case-control study. The differences in protein expression levels of MST1 and MST2 between normal tissue and cancer tissue will also be elucidated, and the relationships between susceptible SNP and the protein levels will be investigated. Our findings will provide experimental data and theoretical basis for prevention, precision medicine, gene therapy, and new drug development of gastric cancer.

胃癌是复杂的多基因疾病，其癌变是一个渐进的多步骤、多阶段过程。胃癌进展的疾病模型包括了幽门螺杆菌感染、慢性萎缩性胃炎、肠上皮化生、不典型增生、胃癌等阶段。MST信号通路是进化上高度保守的能够调控细胞的增殖、分化、凋亡，进而调控组织稳定和器官生长的通路。MST信号通路是一肿瘤抑制通路，成员的功能异常和癌症的发生发展相关。研究显示这一通路的许多成员参与了胃癌的发生发展。本项目用病例-对照关联研究的方法，在包头地区汉族人群中研究了MST1和MST2基因的调控区的以及文献报道的可能和人类疾病相关的一些标记单核苷酸多态性（Tag-SNP）与幽门螺杆菌感染、非贲门胃癌发病风险的关系。结果显示，在427例正常对照中，幽门螺杆菌感染的阳性率为47.3%。在正常对照中，MST2基因的SNP rs10955176在共显性、隐性和超显性模型中都与幽门螺杆菌感染关联，其中隐性模型最适合；其余SNP位点与幽门螺杆菌感染没有关联。在381例非贲门胃癌病人和427例正常对照中检测了研究的SNPs与非贲门胃癌发病风险的关系，发现MST2基因SNP rs7827435在共显性、隐性和超显性模型中都与非贲门胃癌的发病风险关联，但隐性模型最适合；其余SNP位点与非贲门胃癌发病风险没有关联。MST1基因单体型与幽门螺杆菌感染和非贲门胃癌的发病风险没有关联，MST2基因的SNP没有形成单体型块。研究显示MST1和MST2在非贲门胃癌组织中的表达水平显著低于癌旁正常组织，差异有统计学意义；但研究的SNPs与蛋白表达水平没有关联。研究结果为胃癌预防措施的制订和精准医疗、基因治疗、开发新药积累了实验参考和理论依据。