MRPL3 is identified as a prognostic biomarker and therapeutic target in lung adenocarcinoma via a lactylation-disulfidptosis gene signature model and experimental validation.

Background: Lung adenocarcinoma (LUAD), the most prevalent histological subtype of lung cancer, is a leading cause of global cancer mortality. Its pronounced heterogeneity poses a critical challenge, creating an urgent need for reliable biomarkers to accurately predict patient prognosis. Here, we focus on two critical tumor-promoting factors: lactylation and disulfidptosis. Methods: Differential expression analysis, correlation analysis, and univariate survival analysis were performed using gene expression profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts to screen differentially expressed genes (DEGs), lactylation and disulfidptosis related genes (LDRGs), and prognosis-related genes (PGs). A prognostic model was constructed via LASSO regression, with its efficacy evaluated using calibration plots and decision curve analysis (DCA).The regulatory role of mitochondrial ribosomal protein large subunit 3 (MRPL3) in lung adenocarcinoma (LUAD) progression was validated through both Results: This model demonstrated reliable predictive performance across the testing set, validation set, and external validation cohorts. MRPL3 was found to be overexpressed in LUAD tissues and correlated with poor prognosis, advanced tumor stage, and an immunosuppressive tumor microenvironment. Conclusion: Collectively, this study establishes a robust prognostic model for LUAD and clarifies MRPL3's role in regulating glycolytic-lactate metabolism and disulfidptosis to influence tumor progression and immune microenvironment remodeling. These findings provide a novel potential target and theoretical basis for LUAD prognosis assessment and targeted therapy.