我国是胃癌最为高发的国家之一，化疗耐药是影响胃癌综合治疗疗效的严重问题。应激颗粒(stress granules, SGs)的形成是机体应对外来打击时最为重要的自我防御和适应性调节方式之一，其重要组件G3BP1被认为可以抑制氧化酶系统依赖的细胞凋亡。YWHAZ是一个重要的促癌基因，在细胞周期和细胞凋亡的调控中发挥重要作用。我们的前期研究发现，G3BP1不仅在胃癌中高表达，并且与胃癌的增殖转移及不良预后密切相关。同时还发现胃癌细胞中G3BP1与YWHAZ存在相互作用，并且与细胞凋亡和化疗耐药相关。因此，我们认为应激颗粒可能基于G3BP1/YWHAZ通路调控胃癌化疗耐药。本申请项目拟在前期实验基础上，在化疗后机体应激颗粒的形成和作用层面，研究G3BP1参与胃癌化疗耐药的调控及其分子机制，并将基础试验研究结果与临床大数据分析结合，筛选出化疗耐药相关的分子生物标志物，建立个体化的化疗疗效预测模型。

China is one of the countries with the highest incidence of gastric cancer. Chemotherapy resistance is a major reason for the poor efficiency of gastric cancer treatment. The formation of stress granules is one the most important self-defensive and adaptive regulating patterns after stress. Ras-GTPase-activating protein SH3 domain-binding protein1, G3BP1, one of the most important part of stress granules, was supposed to inhibit apoptosis induced by oxidase system. YWHAZ is an oncogene, which plays an important role in modulating cell cycle and apoptosis. In our previous study, we found that G3BP1 was increased in tumor tissue. It was associated with tumor proliferation, metastasis and poor prognosis. We also found the interaction between G3BP1 and YWHAZ, which was associated with apoptosis and chemotherapy resistance. So we proposed a hypothesis that stress granules would modulate chemotherapy resistance in gastric cancer via G3BP1/YWHAZ signal way. This project proposal for grant application is designed on the basis of our previous work to elucidate the functional role and molecular mechanism of G3BP1 modulating chemotherapy. We would combine the results from basic research and clinical big data to select biomarkers related to chemotherapy resistance and establish an individualized model to predict benefits from chemotherapy.