Prognostic significance of genes associated with disulfidptosis in lung squamous cell carcinoma.

BACKGROUND: This study aimed to investigate the relationship between disulfidptosis-related genes (DRGs) and lung squamous cell carcinoma (LUSC). METHODS: Using the TCGA-LUSC dataset, WGCNA identified LUSC-related genes, and hub genes were obtained after intersecting these with DRGs. Consensus clustering analysis divided LUSC patients into different subtypes and differentially expressed genes were then identified. LASSO-Cox regression was applied to establish a prognostic model, followed by analyses of immune cell infiltration and drug sensitivity. Finally, in vitro experiments confirmed the results of bioinformatics analysis. RESULTS: After intersecting 9,157 LUSC-related genes with 24 DRGs, 12 hub genes were identified. Two subtypes (Cluster 1 and Cluster 2) for LUSC were recognized, and 219 differentially expressed genes were screened. A prognostic model was constructed based on 7 genes (CD300LG, PCDHGA12, HPD, KANK4, PPBP, ZCCHC5, and CSMD3), with good predictive ability. Neutrophils, plasma cells, T cells CD4 memory resting, and T cells follicular helper displayed significant differences between different risk groups and subtypes. ZCCHC5 and PCDHGA12 were negatively correlated with all 20 screened drugs. In vitro experiments confirmed the occurrence of disulfidptosis and the levels of prognostic genes in LUSC. CONCLUSION: The study identified two LUSC subtypes and established a 7-gene prognostic model based on DRGs, which can be used as a new prognostic tool for LUSC. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13019-026-03920-5.