Department of Laboratory, Hexian Memorial Hospital of Panyu District, No. 2, Qinghe East Road, Panyu District, Guangzhou, 511400, China.
Department of Gastrointestinal Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, China.
Sci Rep. 2023 Nov 22;13(1):20443. doi: 10.1038/s41598-023-47631-6.
Fatty acid metabolism (FAM) is associated with prognosis and immune microenvironment remodeling in many tumors. It is currently unknown how FAM affects the immunological microenvironment and prognosis of Gastric cancer (GC). Therefore, the current work aims to categorize GC samples based on the expression status of genes involved in FAM and to identify populations that might benefit from immunotherapy. In total, 50 FAM genes associated with overall survival (OS) were determined through univariate Cox proportional hazard regression analysis by mining the public TCGA and GEO databases. The GSE84437 and TCGA-STAD cohort samples were divided into two clusters using the "NMF" R package. According to the survival curve, patients in Cluster-1 showed considerably longer OS than those in Cluster-2. Patients in Cluster-1 exhibited earlier T stages, more intestinal GCs, and were older. MSI molecular subtypes were mainly distributed in Cluster-1, while GS molecular subtypes were distributed primarily in Cluster-2. There were 227 upregulated and 22 down-regulated genes (logFC > 1 or logFC < - 1, FDR < 0.05) in Cluster-2 compared with Cluster-1. One hub module (edges = 64, nodes = 12) was identified with a module score of 11.636 through Cytoscape plug-in MCODE. KEGG and GO analysis showed that the hub genes were associated with the cell cycle and cell division. Different immune cell infiltrates profile, and immune pathway enrichment existed between the subtypes. In conclusion, the current findings showed that practically all immunological checkpoint and immunoregulatory genes were elevated in patients with Cluster-2 GC, indicating that FAM subtypes may be crucial in GC immunotherapy.
脂肪酸代谢（FAM）与许多肿瘤的预后和免疫微环境重塑有关。目前尚不清楚 FAM 如何影响胃癌（GC）的免疫微环境和预后。因此，目前的工作旨在根据涉及 FAM 的基因的表达状态对 GC 样本进行分类，并确定可能受益于免疫治疗的人群。通过挖掘公共 TCGA 和 GEO 数据库，通过单变量 Cox 比例风险回归分析确定了与总生存期（OS）相关的 50 个 FAM 基因。使用“NMF”R 包将 GSE84437 和 TCGA-STAD 队列样本分为两个簇。根据生存曲线，Cluster-1 中的患者 OS 明显长于 Cluster-2 中的患者。Cluster-1 中的患者表现出更早的 T 期、更多的肠型 GC 和更年长。MSI 分子亚型主要分布在 Cluster-1 中，而 GS 分子亚型主要分布在 Cluster-2 中。与 Cluster-1 相比，Cluster-2 中有 227 个上调基因和 22 个下调基因（logFC > 1 或 logFC < -1，FDR < 0.05）。通过 Cytoscape 插件 MCODE 鉴定出一个模块评分为 11.636 的 1 个枢纽模块（边=64，节点=12）。KEGG 和 GO 分析表明，枢纽基因与细胞周期和细胞分裂有关。两种亚型之间存在不同的免疫细胞浸润谱和免疫途径富集。总之，目前的研究结果表明，Cluster-2 GC 患者的几乎所有免疫检查点和免疫调节基因都升高，表明 FAM 亚型在 GC 免疫治疗中可能至关重要。
