Identification Cuproptosis-related Genes Signature to Predict the Prognosis of Lung Cancer

Cuproptosis, a recently characterized form of regulated cell death driven by copper ions, has been implicated in cancer progression, yet its prognostic significance in lung adenocarcinoma (LUAD) remains unclear. In this study, we explored the expression patterns and prognostic relevance of 19 cuproptosis-related genes (CuRGs) using multiple public datasets. Consensus clustering analysis stratified LUAD patients into two distinct molecular subtypes with significant differences in clinical outcomes and immune characteristics. Differentially expressed genes (DEGs) between the two subtypes were identified, and functional enrichment analysis revealed significant associations with immune pathways. A prognostic risk signature (CuRG_score) comprising five genes was constructed using LASSO-Cox regression and validated across three independent GEO datasets. The CuRG_score effectively stratified patients into high- and low-risk groups with significant differences in overall survival. The AUC values were 0.761, 0.618, and 0.642 across the datasets, respectively, demonstrating strong predictive power. Further analysis revealed that high-risk patients exhibited immunosuppressive features, including lower infiltration of CD8+T cells and NK cells. Moreover, immune checkpoint expression and immunophenoscore (IPS) analysis suggested that low-risk patients may benefit more from immunotherapy. In conclusion, our study identifies a novel CuRG-based molecular signature that serves as a robust predictor of LUAD prognosis and offers potential guidance for personalized immunotherapy strategies.