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

Abstract

e20502 Background: Research has increasingly shown that lipid metabolism contribute to lymph node metastasis and the progression of cancer. This study investigates the role of lipid metabolism in lymph node metastasis (LNM) of lung adenocarcinoma (LUAD). Methods: We gathered clinicopathological data and RNA-sequencing information from LUAD patients using the TCGA and GEO databases. We identified 189 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: We identified a three-gene lipid metabolic signature (GPD1L, SPHK1, and ST3GAL4) associated with tumor progression in LUAD with LNM. We discovered a three-gene lipid metabolic signature (GPD1L, SPHK1, ST3GAL4) associated with LNM in LUAD. High-risk patients had worse overall survival, increased M0 macrophages, degranulating mast cell infiltration, non-responsive immunotherapy outcomes, and TKI drug resistance. High-risk patients also exhibited higher tumor mutation burdens and PDL-1 expression, suggesting potential benefits from combined immunotherapy and LMRG-targeted therapy. Differentially expressed genes in the high-risk group were enriched in the reactive oxygen species pathway. Conclusions: Our findings offer new insights into the molecular mechanisms and precision therapies for regional metastasis in LUAD related to lipid metabolism. RNA-seq data for 21-differential (Top 10) expression genes from TCGA database. logFC AveExpr t P.Value adj.P.Val B GLA 4.518085151 15.99523125 4.09640666 4.92E-05 0.009306128 1.74272825 CHKA -2.305978036 10.14179057 -3.51115756 0.000488211 0.046135986 -0.253610135 SPTLC2 -1.550602889 10.57017911 -3.181292727 0.001561022 0.098344383 -1.250677285 GPD1L -2.724731165 14.68046025 -2.990476429 0.002928352 0.119257184 -1.784553554 ALDH1B1 2.8798922 14.6613991 2.967209901 0.003154952 0.119257184 -1.847482865 B4GALT2 2.295863715 18.02370103 2.801016218 0.005299554 0.148776115 -2.283220656 SPHK1 1.012794176 4.062592604 2.552565108 0.011001314 0.231027601 -2.889328347 B3GNT3 5.417914701 22.51836702 2.479618477 0.013493941 0.239387084 -3.05691525 GBA 1.873790668 18.89787698 2.46804016 0.013932582 0.239387084 -3.083080645