Integrated Analysis Identifies a TRPM4-Related Sodium Overload Signature with Prognostic Value and Experimentally Validates RNPEPL1 in Lung Adenocarcinoma

Background: Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide, and effective biomarkers for prognosis and therapeutic guidance are still lacking. TRPM4, a sodium-related ion channel, has been implicated in tumor progression; however, its role in LUAD, particularly at the single-cell level, remains unclear. Methods: Single-cell RNA sequencing data were used to analyze the cellular distribution of TRPM4 in LUAD. TRPM4-related genes were identified through correlation analysis in the TCGA cohort, followed by construction of a prognostic model using Cox and LASSO regression analyses. The model was validated in an independent GEO dataset. Functional enrichment and drug sensitivity analyses were performed to explore the underlying mechanisms and therapeutic implications. Random forest analysis was applied to identify key genes, and in vitro experiments were conducted to validate their biological functions. Results: A TRPM4-related prognostic signature was established, demonstrating robust predictive performance in both training and validation cohorts. High-risk patients were characterized by activation of cell cycle and DNA replication pathways, showing differences in computationally predicted sensitivity to multiple chemotherapeutic and targeted agents. Furthermore, RNPEPL1 was identified as a key gene and experimentally validated to promote LUAD cell proliferation, migration, and invasion. Conclusions: The TRPM4-related signature and RNPEPL1 may provide novel insights for risk stratification and personalized therapeutic strategies.