Construction and validation of a prognostic model for lung adenocarcinoma based on necrotic cell death triggered by sodium overload-related coexpressed genes.

Introduction: The aim of this study was to explore the prognostic significance of necrotic cell death triggered by sodium overload (NECSO)-related genes in lung adenocarcinoma (LUAD) and construct a prognostic model with high predictive efficiency. The findings will enable a precise stratification of the prognostic risk of patients with LUAD. Analysis of the constructed prognostic model, immune cell infiltration, and tumor mutational burden (TMB) will facilitate the development of individualized precision medical protocols. Methods: Based on the LUAD data obtained from TCGA and GEO databases, a prognostic prediction model for LUAD containing 15 key genes (including arginyl aminopeptidase like 1 [RNPEPL1] and beta-1,3-N-acetylglucosaminyltransferase 3 [B3GNT3]) coexpressing with the key NECSO gene, TRPM4, was established. Results: Risk score was identified as an independent prognostic factor. High-risk patients had the following characteristics: high frequency of mutations in TP53 and TTN genes, high TMB, high number of immunosuppressive cells with impaired immune cell function, and abnormally active metabolism. Nomograms developed by integrating clinical features and risk scores displayed high predictability. Discussion: The findings provide new molecular markers and potential therapeutic targets for the prognosis of LUAD and lay a theoretical foundation for the development of therapeutic approaches targeting the NECSO mechanism in patients with LUAD.