[Immune-related genes and their determined immune cell microenvironment to predict the prognosis of gastric adenocarcinoma].

Objective: Through bioinformatics analysis to screen key immune-related genes (IRGs) and cancer-related pathways in gastric adenocarcinoma (GAC) therapy, combining immune cell microenvironment to predict the prognosis of GAC. Methods: RNA sequencing and clinical data were obtained from public databases. Differentially expressed IRGs between GAC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analyses were applied to screen survival-associated IRGs. Then, we established the risk signature model and found another database for external validation. In addition, we explored the relationship with the immune cell microenvironment in each GAC sample using CIBERSORT algorithms. Results: A total of 78 differentially expressed IRGs were screened, including 47 up-regulated and 31 down-regulated genes. Subsequently, a five-IRGs signature (BMP8A、MMP12、NRG4、S100A9 and TUBB3) was significantly associated with the overall survival of GAC patients. Survival analysis indicated that patients in the high-risk group have a poor prognosis. The results of the multivariate analysis revealed that the risk score was an independent prognostic factor. Further analysis showed that the prognostic model had excellent predictive performance in both TCGA and GEO validated cohorts. Besides, the results of tumor-infiltrating immune cell analysis indicated that the risk score could reflect the status of the tumor immune microenvironment. Conclusion: BMP8A, MMP12, NRG4, S100A9 and TUBB3 with the risk signature model are associated with prognosis in patients with GAC, combined with tumor-infiltrating immune cells to provide new markers for immunotherapy in GAC.目的： 通过生物信息学分析筛选胃腺癌的差异表达免疫相关基因及癌症相关通路，结合免疫细胞微环境预测胃腺癌的预后。 方法： 从癌症基因图谱数据库（TCGA）和基因表达（GEO）数据库下载RNA测序数据和临床数据通过生物信息学分析，获得343例胃腺癌组织和30例正常组织中差异表达的免疫相关基因；根据单因素和多因素Cox回归分析筛选与生存相关的免疫相关基因并构建预后风险模型，并使用CIBERSORT算法探索免疫相关基因与免疫细胞微环境的关系。 结果： TCGA数据库中共获得8 202个差异表达基因，其中有4 908个上调差异表达基因、3 294个下调差异表达基因。GSE118916中共获得1 762个差异表达基因，其中909个上调差异表达基因、853个下调差异表达基因。最终获得差异表达免疫相关基因（IRG）共78个，其中47个上调基因、31个下调基因；其中BMP8A、MMP12、NRG4、S100A9和TUBB3证实与胃腺癌患者的生存显著相关。生存分析表明高风险组预后差，多因素分析显示风险评分是独立的预后因素，并在TCGA数据集和GEO外部验证集都有良好预测性能。此外，肿瘤浸润性免疫细胞分析结果表明，该风险评分可以反映肿瘤免疫细胞微环境的状态。 结论： BMP8A、MMP12、NRG4、S100A9和TUBB3及其构建的风险模型与胃腺癌患者的预后相关，结合肿瘤浸润免疫细胞，为胃腺癌的免疫治疗提供新的靶点。.