Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Department of Allergy, The Affiliated Hospital of Qingdao University.
J Immunother. 2023 Oct 1;46(8):323-332. doi: 10.1097/CJI.0000000000000481. Epub 2023 Jul 19.
Prognostic signatures related to the efficacy of immunotherapy have not been determined in gastric cancer (GC). We identified the differentially expressed genes between the CR/PR and SD/PD groups with the R package "limma" (false discovery rate <0.05) in the IMvigor210 data set. The GSE13861 (n=65), GSE15459 (n=192), GSE26899 (n=93), GSE26901 (n=109), GSE28541 (n=40), GSE34942 (n=56), and GSE62254 (n=300) cohorts were merged into a training cohort (n=855). Univariate Cox regression analysis, LASSO penalized Cox regression analysis, and multivariate Cox regression analysis were jointly applied to construct the prognostic model. The Cancer Genome Atlas (TCGA)-STAD (n=371), GSE84437 (n=433), GSE26253 (n=432), and IMvigor210 (n=348) cohorts were utilized for external validation. The GC patients were divided into 16 subgroups according to clinical features for universal applicability validation. Repeated validation confirmed that the overall survival of the high-risk (HR) group was significantly reduced compared with that of the low-risk (LR) group. The HR group showed a higher infiltration abundance of regulatory T cells, macrophages, T follicular helper cells, and natural killer T cells, whereas the infiltration levels of activated CD4 T cells and monocytes were upregulated in the LR group. The calcium, TGF-β, MAPK, Hedgehog, and KRAS signaling pathways were overactivated in the HR group, while the hallmarks related to DNA damage repair and metabolism were enriched in the LR group. In addition, the LR group had high tumor mutation burden, FLG, and OBSCN mutations. A prognostic risk classifier for GC patients was identified and validated by carrying out a multicenter retrospective study.
在胃癌（GC）中，尚未确定与免疫治疗疗效相关的预后标志物。我们使用 R 包“limma”（错误发现率<0.05）在 IMvigor210 数据集确定了 CR/PR 和 SD/PD 组之间的差异表达基因。GSE13861（n=65）、GSE15459（n=192）、GSE26899（n=93）、GSE26901（n=109）、GSE28541（n=40）、GSE34942（n=56）和 GSE62254（n=300）队列被合并到一个训练队列（n=855）中。进行单因素 Cox 回归分析、LASSO 惩罚 Cox 回归分析和多因素 Cox 回归分析，共同构建预后模型。癌症基因组图谱（TCGA）-STAD（n=371）、GSE84437（n=433）、GSE26253（n=432）和 IMvigor210（n=348）队列用于外部验证。根据临床特征将 GC 患者分为 16 个亚组进行普遍适用性验证。重复验证证实，高危（HR）组的总生存率明显低于低危（LR）组。HR 组显示调节性 T 细胞、巨噬细胞、滤泡辅助 T 细胞和自然杀伤 T 细胞的浸润丰度较高，而 LR 组中激活的 CD4 T 细胞和单核细胞的浸润水平上调。HR 组中钙、TGF-β、MAPK、Hedgehog 和 KRAS 信号通路过度激活，而 LR 组中与 DNA 损伤修复和代谢相关的特征富集。此外，LR 组具有高肿瘤突变负担、FLG 和 OBSCN 突变。通过进行多中心回顾性研究，鉴定并验证了 GC 患者的预后风险分类器。
