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

Abstract

Simple Summary Lung adenocarcinoma remains difficult to manage because patients with similar clinical characteristics can have markedly different outcomes and treatment responses. In this study, we investigated TRPM4, an ion channel associated with sodium overload-related cell death, using single-cell and bulk RNA sequencing data. We developed a TRPM4-related gene signature that successfully separated patients into high- and low-risk groups and predicted overall survival in both training and independent validation cohorts. High-risk tumors showed increased activity of cell cycle and DNA replication pathways and distinct predicted responses to several anticancer drugs. RNPEPL1 was identified as a key gene within the signature. Laboratory experiments showed that reducing RNPEPL1 expression inhibited lung adenocarcinoma cell growth, migration, invasion, and tumor formation, while also increasing sensitivity to selected targeted drugs. These findings may support improved prognostic assessment and help guide future personalized treatment strategies for lung adenocarcinoma.