申请人在前期青年项目资助下的研究发现：胃癌患者BRCA1表达水平可预测该患者是否可从含多西紫杉醇的化疗方案中获益，BRCA1高表达者生存期为低表达者的2.6倍。越来越多的研究证明多个分子组合可进一步更加精准地预测抗肿瘤药物效果。本项目拟将近年个体化治疗的基础研究成果与前期研究基础进行整合并向临床转化：在肿瘤组织及对应正常组织检测DNA损伤修复途径BRCA1上游分子（MDC1/UBC9/MMSET/53BP1）、BRCA1交互网络分子（EZH2/AEG-1/BIM）、HIPPO途径关键分子（β-TRCP/TAZ/AXL）表达水平，筛选肿瘤差异表达基因，并将基因水平与铂类/紫杉类药物敏感性进行分析，同时在有随访资料的接受铂类/紫杉类化疗的胃癌患者中进一步验证，建立药物疗效预测分子组合，分析其与化疗疗效及预后的关系，寻求胃癌个体化疗的更为精确预测分子指标，为后续开展前瞻性临床试验提供科学依据。

Our previous study supported by NSFC demonstrated a subgroup of gastric cancer patients could benefit from docetaxel-based chemotherapy. Overall survival time is 2.6-fold times in patients with high BRCA1 levels when compared with those having low BRCA1 levels. Accumulated evidence showed a model including several biomarkers could predict the chemosensitivity more precisely. In this project, we aim to examine genes involving in DNA repair pathway as BRCA1 upstreams (MDC1、UBC9、MMSET、53BP1), BRCA1 modulators (EZH2、AEG-1、BIM), and HIPPO pathway (β-TRCP、TAZ、AXL) in gastric cancer samples and paired normal tissues, and to screen the tumor-specific genes and correlate those genes with chemosensitivity to platinum and taxanes. We will also analyze those gene levels with the outcome in group of gastric cancer patients receiving oxalipatin or docetaxel-based chemotherapy regimens. This project might establish a response index to chemosensitivity of platinum and taxanes and provide evidence for the following perspective clinical trials.