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

BackgroundLung 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.MethodsDifferential 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 in vivo and in vitro experiments.ResultsThis 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.