Prognostic value of a lactate metabolism gene signature in lung adenocarcinoma and its associations with immune checkpoint blockade therapy response

Lung adenocarcinoma (LUAD) is a study that examines the prognostic value of lactate metabolism genes in tumor cells, which are associated with clinical prognosis. We analyzed the expression and clinical data for LUAD from The Cancer Genome Atlas database, using the GSE68465 dataset from the Gene Expression Omnibus and the MSigDB database. LASSO Cox regression and stepwise Cox regression were used to identify the optimal lactate metabolism gene signature. Differences in immune infiltration, tumor mutation burden (TMB), and response to immune checkpoint blockade (ICB) therapy were evaluated between groups. LASSO and Cox regression analyses showed an eight-lactate metabolism gene signature for model construction in both TCGA cohort and GSE68465 data, with higher survival outcomes in high-risk groups. The lactate metabolism risk score had an independent prognostic value (hazard ratio: 2.279 [1.652-3.146], P < .001). Immune cell infiltration differed between the risk groups, such as CD8+ T cells, macrophages, dendritic cells, mast cells, and neutrophils. The high-risk group had higher tumor purity, lower immune and stromal scores, and higher TMB. High-risk samples had high tumor immune dysfunction and exclusion (TIDE) scores and low cytolytic activity (CYT) scores, indicating a poor response to ICB therapy. Similarly, most immune checkpoint molecules, immune inhibitors/stimulators, and major histocompatibility complex (MHC) molecules were highly expressed in the high-risk group. The 8-lactate metabolism gene-based prognostic model predicts patient survival, immune infiltration, and ICB response in patients with LUAD, driving the development of therapeutic strategies to target lactate metabolism.