Sun Weijie, Xia Yanhong, Jin Feifan, Cao Jinghao, Wu Gaoping, Li Keyi, Yu Yanhua, Wu Yunyi, Ye Gaoqi, Xu Ke, Liu Dengpan, Jin Weidong
Department of Clinical Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Procurement Center, Hangzhou Children's Hospital, Hangzhou, Zhejiang, China.
Discov Oncol. 2025 Jan 4;16(1):6. doi: 10.1007/s12672-025-01745-7.
Gastric cancer (GC), one of the most common and heterogeneous malignancies, is the second leading cause of cancer death worldwide and is closely related to dietary habits. Fatty acid is one of the main nutrients of human beings, which is closely related to diabetes, hypertension and other diseases. However, the correlation between fatty acid metabolism and the development and progression of GC remains largely unknown. Here, we profiled the genetic alterations of fatty acid anabolism-related genes (FARGs) in gastric cancer samples from the TCGA cohort and GEO database to evaluate the possible relationships and their internal regulatory mechanism. Through consistent clustering and functional enrichment analysis, three distinct fatty acid anabolism clusters and three gene subtypes were identified to participate in different biological pathways, and correlated with the characteristics of immune cell infiltration and clinical prognosis. Importantly, a distinctive FA-score was constructed through the principal component analysis to quantify the characteristics of fatty acid anabolism in each GC patient. Further analysis showed patients grouped in the high FA-score group were characterized with greater tumor mutational burden (TMB) and higher microsatellite stability (MSI-H), which may be more aeschynomenous to immunotherapy and had a favorable prognosis. Altogether, our bioinformatics analysis based on FARGs uncovered the potential roles of fatty acid metabolism in GC, and may provide newly prognostic information and novel approaches for promoting individualized immunotherapy in patients with GC.
胃癌（GC）是最常见且异质性最强的恶性肿瘤之一，是全球癌症死亡的第二大主要原因，并且与饮食习惯密切相关。脂肪酸是人类的主要营养物质之一，与糖尿病、高血压等疾病密切相关。然而，脂肪酸代谢与GC发生发展之间的相关性在很大程度上仍不清楚。在此，我们分析了来自TCGA队列和GEO数据库的胃癌样本中脂肪酸合成代谢相关基因（FARGs）的基因改变，以评估可能的关系及其内在调控机制。通过一致性聚类和功能富集分析，鉴定出三个不同的脂肪酸合成代谢簇和三种基因亚型，它们参与不同的生物学途径，并与免疫细胞浸润特征和临床预后相关。重要的是，通过主成分分析构建了一个独特的FA评分，以量化每个GC患者的脂肪酸合成代谢特征。进一步分析表明，高FA评分组的患者具有更高的肿瘤突变负荷（TMB）和更高的微卫星稳定性（MSI-H），这可能对免疫治疗更敏感且预后良好。总之，我们基于FARGs的生物信息学分析揭示了脂肪酸代谢在GC中的潜在作用，并可能为促进GC患者的个体化免疫治疗提供新的预后信息和新方法。
