Novel lipid metabolism-related gene signature associated with clinical and immune features in lung adenocarcinoma patients experiencing lymph node metastasis

Background: Research has increasingly shown that lipid metabolism contributes to lymph node metastasis (LNM) and the progression of cancer. This study investigates the role of lipid metabolism in LNM of lung adenocarcinoma (LUAD). Methods: We gathered clinicopathological data and RNA-sequencing information from LUAD patients using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We identified differentially expressed lipid metabolism-related genes (LMRGs) in LUAD with and without LNM. Using a prognostic risk scoring system, we correlated LMRGs with clinicopathological outcomes, genomic alterations, immune features, immunotherapy responses, and drug susceptibility. Results: ) associated with LNM and tumor progression was identified. High-risk patients exhibited worse overall survival (OS), increased infiltration of M0 macrophages and degranulating mast cells, and were more likely to be non-responsive to immunotherapy. Additionally, the high-risk group showed higher tumor mutation burden (TMB) and programmed death-ligand 1 (PD-L1) expression, suggesting a potential benefit from combined immunotherapy and LMRG-targeted therapy. Differentially expressed genes (DEGs) in the high-risk group were enriched in the reactive oxygen species pathway. Conclusions: Our findings provide new insights into the molecular mechanisms underlying regional metastasis in LUAD related to lipid metabolism and highlight the potential for precision therapies targeting this pathway.