Regulation of Fatty Acid Metabolism Defines Distinct Molecular Subtypes in Stomach Adenocarcinoma: Implications for Tumor Microenvironment and Precision Therapeutics

Introduction

Stomach adenocarcinoma (STAD) is a major global gastrointestinal malignancy, significantly impacting morbidity and mortality rates worldwide. Advances in lipidomics and metabolomics shed light on fatty acid metabolism's role in various malignancies, including STAD. However, the specific influence of fatty acid metabolism-related genes (FAMGs) on STAD's therapeutic response remains unclear.

Methods

This work merged high-dimensional datasets from TCGA and GEO to assess FAMGs' predictive value in STAD. These datasets encompassed molecular variables (mRNAsi, genomic mutations, CNV, TMB), enabling the construction of a robust predictive model via Lasso regression. Co-expression network analysis delineated FAMGs' functional roles and therapeutic implications.

Results

FAMGs were consistently overexpressed in high-risk STAD, suggesting their potential as prognostic biomarkers. High-risk groups displayed enrichment in immunological and tumor-associated pathways. Candidate genes (APOD, FLRT2, MMRN1, CD36) surfaced as potential contributors to STAD's oncogenic basis. Immunological processes and m6a gene expression varied across risk strata, emphasizing divergent prognostic trajectories. The predictive model showed strong associations with genomic features and drug susceptibility profiles.

Discussion

FAMGs play a crucial role in STAD pathogenesis and clinical course. The derived FAMG signature serves as a potent prognostic tool and paves the way for targeted therapeutic research in STAD.