Table1_Development of a Novel Immune-Related Gene Signature to Predict Prognosis and Immunotherapeutic Efficiency in Gastric Cancer.DOCX

Background: Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of tumor-related deaths globally. Herein, we attempted to build a novel immune-related gene (IRG) signature that could predict the prognosis and immunotherapeutic efficiency for GC patients.Methods: The mRNA transcription data and corresponding clinical data of GC were downloaded from The Cancer Genome Atlas (TCGA) database as the training group and the GSE84437 data set as the testing cohort, followed by acquisition of IRGs from the InnateDB resource and ImmPort database. Using the univariate Cox regression analysis, an IRG signature was developed. Several immunogenomic analyses were performed to illustrate the associations between the immune risk score and tumor mutational burden, immune cell infiltrations, function of immune infiltration, clinical characteristics, immune subtype, and immunotherapeutic response.Results: The analysis of 343 GC samples and 30 normal samples from the TCGA database gave rise to 8,713 differentially expressed genes (DEGs) and 513 differentially expressed immune-related genes (DEIRGs) were extracted. The novel IRG signature contained eight DEIRGs (FABP4, PI15, RNASE2, CGB5, INHBE, RLN2, DUSP1, and CD36) and was found to serve as an independent predictive and prognostic factor for GC. Then, the GC patients were separated into the high- and low-risk groups based on the median risk score, wherein the low-risk group presented a better prognosis and was more sensitive to immunotherapy than did the high-risk group. According to the time-dependent ROC curves and AUCs, the immunotherapeutic value of the signature was better than the Tumor Immune Dysfunction and Exclusion (TIDE) and T-cell inflammatory signature (TIS) scores. In addition, the AUCs of the risk score for predicting 1-, 2-, and 3-year OS were 0.675, 0.682, and 0.710, respectively, which indicated that the signature had great predictive power.Conclusion: This study presents a novel IRG signature based on the tumor immune microenvironment, which could improve the prediction of the prognosis and immunotherapeutic efficiency for GC patients. The powerful signature may serve as novel biomarkers and provide therapeutic targets for precision oncology in clinical practice.

背景：胃腺癌（GC）是全球第五位常见的恶性肿瘤，同时也是肿瘤相关死亡的首要原因。本研究旨在构建一个能够预测胃腺癌患者预后及免疫治疗效率的新型免疫相关基因（IRG）特征。方法：从癌症基因组图谱（TCGA）数据库中下载了胃腺癌的mRNA转录数据和相应的临床数据作为训练组，以及GSE84437数据集作为测试队列。随后，从InnateDB资源和ImmPort数据库中获取了IRGs。通过单因素Cox回归分析，开发了一个IRG特征。进行了多项免疫基因组学分析，以阐述免疫风险评分与肿瘤突变负荷、免疫细胞浸润、免疫浸润功能、临床特征、免疫亚型和免疫治疗反应之间的关联。结果：对TCGA数据库中的343个胃腺癌样本和30个正常样本进行分析，产生了8,713个差异表达基因（DEGs），并从中提取了513个差异表达免疫相关基因（DEIRGs）。该新型IRG特征包含八个DEIRGs（FABP4、PI15、RNASE2、CGB5、INHBE、RLN2、DUSP1和CD36），并被发现可作为胃腺癌独立的预测和预后因素。随后，根据中位风险评分将胃腺癌患者分为高风险组和低风险组，其中低风险组预后较好，对免疫治疗的敏感性高于高风险组。根据时间依赖性ROC曲线和AUC值，该特征的免疫治疗价值优于肿瘤免疫功能障碍和排除（TIDE）评分以及T细胞炎症特征（TIS）评分。此外，预测1年、2年和3年总生存率的AUC值分别为0.675、0.682和0.710，这表明该特征具有强大的预测能力。结论：本研究提出了一种基于肿瘤免疫微环境的IRG特征，该特征能够提高胃腺癌患者预后及免疫治疗效率的预测。这一强有力的特征可能作为新的生物标志物，并为临床实践中的精准肿瘤学提供治疗靶点。