Background <p>Sodium overload-induced cell death is a novel mode of cell death that differs from other modes and is a very promising new target for cancer therapy. In addition, sodium overload-induced cell death plays a crucial role in cancer progression and patient prognosis. Therefore, our study aims to establish a survival prediction model for patients with lung adenocarcinoma (LUAD) based on related genes, exploring the immune landscape and providing new insights for future individualized treatment protocols.</p> Method <p>We analyzed the expression and clinical significance of TRPM4-related genes in LUAD using data from TCGA and GEO databases. We used transcriptomics, immune infiltration assays, and spatial transcriptomics (ST). Kaplan-Meier survival analysis was used to assess the relationship between TRPM4-related genes and prognosis. Enrichment analyses identified biological processes and pathways associated with TRPM4 and also assessed its relationship with the immune microenvironment and drug sensitivity.</p> Results <p>We identified 19 oncogenic driver genes and modeled proportional hazard regression. The results showed that the survival rate of the high-risk group was significantly reduced in both the training and testing sets. Additionally, the high-risk group exhibited lower levels of immune cell infiltration and immune checkpoint expression compared to the low-risk group. Based on 19 genes, LMNA, PPP2R1A, and PDXK were identified as key genes by single-cell sequencing and spatial transcriptome sequencing.</p>