胃癌在世界范围内是第二大癌症死亡原因。流行病学研究表明，心理社会应激能促进肿瘤的发生与发展，并显著降低肿瘤患者的5年生存率，但其作用机制尚不明了。本课题组前期在使用N-甲基-N-亚硝脲（MNU）诱导C57BL/6小鼠胃癌模型的基础上，采用束缚小鼠行动来模拟慢性应激刺激，成功建立用于研究慢性应激在胃癌发生过程中的作用的模型，结果提示慢性应激具有明显的促进胃癌发生的作用。进一步通过基因表达谱测序发现，DNA修复机制及免疫微环境异常可能介导了应激相关性胃癌的发生过程。根据前期研究结果，我们提出假说：慢性应激使胃粘膜上皮细胞DNA发生损伤，并降低碱基切除修复途径的修复能力，从而导致基因组不稳定，最终引起细胞恶性转化；另一方面，通过改变免疫微环境，导致恶性细胞的免疫逃逸。本项目将综合运用最新分子生物学技术及生物信息学工具，以揭示慢性应激在胃癌发生过程中的作用及机制，为胃癌的预防和治疗提供新的思路。

Gastric cancer is the second most frequent cause of cancer-related death worldwide. It is confirmed by epidemiologic studies that psychological stress can contribute to the incidence and development of cancer, as well as impact the of 5-year survival rate. However, the underlying mechanism is still unclear. We built an animal model to study the effect of chronic stress on gastric carcinogenesis by treating mice with the combination of MNU and constraint. The results suggested that chronic stress significantly promoted the incidence of gastric cancer. With further gene sequencing test, we found that DNA repair pathway and immune microenviroment dysregulation might be involved. According to the previous foundation, we hypothesize that chronic stress induced DNA damage and DNA repair dysfunction, leading to the genomic instability and final malignant transformation; on the other hand, stress also causes immune escape by changing the immune microenviroment. This study will focus on the effect and underlying mechanism of chronic stress on gastric carcinogenesis with bioinformatics and molecular techniques, which will provide a new for gastric cancer prevention and therapy.