Immunotherapy is remarkably affected by the immune environment of the principal tumor. Nonetheless, the immune environment's clinical relevance in stage IV gastric cancer (GC) is largely unknown. The gene expression profiles of 403 stage IV GC patients in the three cohorts: GEO (Gene Expression Omnibus, GSE84437 (n=292) and GSE62254 (n=77), and TCGA (The Cancer Genome Atlas, n=34) were used in the present study. Using four publicly available stage IV GC expression datasets, 29 immune signatures were expression profiled, and on this basis, we classified stage IV GC. The classification was conducted using the hierarchical clustering method. Three stage IV GC subtypes L, M, and H were identified representing low, medium, and high immunity, respectively. Immune correlation analysis of these three types revealed that Immune H exhibited a better prognostic outcome as well as a higher immune score compared with other subtypes. There was a noticeable difference in the three subgroups of HLA genes. Further, on comparing with other subtypes, CD86, CD80, CD274, CTLA4, PDCD1, and PDCD1LG2 had higher expression in the Immunity H subtype. In stage IV GC, potentially positive associations between immune and pathway activities were displayed, due to the enrichment of pathways including TNF signaling, Th-17 cell differentiation, and JAK-STAT signaling pathways in Immunity H vs Immunity L subtypes. External cohorts from TCGA cohort ratified these results. The identification of stage IV GC subtypes has potential clinical implications in stage IV GC treatment.

中文翻译：

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IV期胃癌的肿瘤微环境特征。

免疫治疗受主要肿瘤免疫环境的影响显着。尽管如此，免疫环境在 IV 期胃癌 (GC) 中的临床相关性在很大程度上是未知的。三个队列中 403 名 IV 期 GC 患者的基因表达谱：GEO（基因表达综合，GSE84437（n=292）和 GSE62254（n=77）和 TCGA（癌症基因组图谱，n=34）用于本研究使用四个公开的IV期GC表达数据集，对29个免疫特征进行了表达分析，并在此基础上，我们对IV期GC进行了分类。使用层次聚类方法进行了分类。IV期GC的三个亚型L，M和 H 分别代表低、中和高免疫力。这三种类型的免疫相关性分析表明，与其他亚型相比，Immune H 表现出更好的预后结果以及更高的免疫评分。HLA 基因的三个亚组存在显着差异。此外，与其他亚型相比，CD86、CD80、CD274、CTLA4、PDCD1和PDCD1LG2在Immunity H亚型中的表达更高。在 IV 期 GC 中，由于免疫 H 与免疫 L 亚型中包括 TNF 信号传导、Th-17 细胞分化和 JAK-STAT 信号传导途径在内的途径的富集，显示了免疫和途径活性之间的潜在正相关。来自 TCGA 队列的外部队列批准了这些结果。IV 期 GC 亚型的鉴定在 IV 期 GC 治疗中具有潜在的临床意义。