Integrated stress response (ISR) genes are implicated in lung adenocarcinoma (LUAD) prognosis, but their clinical utility remains unexplored. This study aims to identify ISR-related prognostic genes and construct a risk model for LUAD survival prediction. LUAD transcriptomic and clinical data were retrieved from public databases. ISR-related genes (ISR-RGs) were screened via differential expression and regression analysis. A risk model and a nomogram integrating clinical indicators were built and validated. Functional enrichment, immune cell infiltration, and RT-qPCR in clinical samples were performed. Five prognostic genes (AGER, GPX3, CCNA2, KCNK3, and CHEK1) were identified. High-risk patients exhibited poorer survival. The nomogram was able to forecast the survival of LUAD well. Genes were functionally linked to cell cycle and DNA replication and correlated with immune cells (e.g., CCNA2 positively with CD4⁺ T cells cor = 0.52; CHEK1 negatively with memory B cells cor = - 0.40). RT-qPCR confirmed dysregulation: AGER, GPX3, and KCNK3 downregulated and CHEK1 and CCNA2 upregulated versus controls. The five prognostic genes pertinent to both LUAD and ISR were identified, and a risk model was constructed for the good prediction of LUAD survival, which offered a fresh outlook for alleviating the poor prognosis of LUAD.
Fu et al. (Fri,) studied this question.