Novel Lipid Metabolism-Related Gene Signature in Lung Adenocarcinoma Patients Experiencing Lymph Node Metastasis

This is the authors' abstract. We don't add key points for this paper.

Accumulating evidence revealed that lipid metabolic reprogramming facilitates lymph node metastasis and cancer progression. This study aimed to perform comprehensive bioinformatic analyses of the lipid metabolism-related impact in lung adenocarcinoma (LUAD) patients experiencing lymph node metastasis (LNM). Clinicopathological information and RNA-sequence data on LUAD patients were collected from the TCGA and GEO databases. Subsequently, 189 differentially expressed lipid metabolism-related genes (LMRGs) were screened for LUAD patients with and without LNM. Based on the risk scoring system related to prognosis, we further correlated the LMRGs with diverse clinicopathological outcomes, genomic alterations, and immune features, as well as immunotherapeutic responses and drug susceptibility. A three-gene lipid metabolic signature (GPD1L, SPHK1, and ST3GAL4) associated with tumor progression in LUAD with LNM was identified. Analyses revealed that the high-risk group had worse overall survival; an increased proportion of M0 macrophages and degranulating mast cell infiltration; increased non-responders to immunotherapy; and resistance to several common TKI drugs. Interestingly, we also found that high-risk patients had higher tumor mutation burdens and PDL-1 expression, suggesting that this subset of patients may benefit from immunotherapy plus LMRG-targeted therapy. Additionally, the results showed that the differential expressed genes (DEGs) of the high-risk group were enriched in the REACTIVE OXYGEN SPECIES pathway. Overall, we identify a lipid metabolic signature that has prognostic value and provides new insights into molecular mechanisms and precision therapies of lipid metabolism-related LUAD regional metastasis.