COPD-Associated PANoptosis Genes Predict Prognosis and Chemotherapy Sensitivity in Lung Squamous Cell Carcinoma

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease that increases the risk of lung squamous cell carcinoma (LUSC). PANoptosis integrates pyroptosis, apoptosis, and necroptosis, but the relationship between COPD-associated PANoptosis genes and LUSC prognosis remains unclear. In this study, we first derived COPD-associated differentially expressed genes from GSE57148 by comparing COPD lung tissues with normal lung tissues and intersected these genes with a curated PANoptosis-associated gene list. The resulting gene set was then applied to TCGA-LUSC, GSE30219, and GSE37745, which were analyzed as LUSC cohorts without confirmed patient-level COPD comorbidity annotation. We evaluated PANoptosis gene expression patterns, performed unsupervised clustering, characterized immune infiltration differences between clusters, and constructed a prognostic signature with external validation. We identified 38 COPD-associated PANoptosis genes with differential expression across tissue types. Two molecular subtypes displayed distinct immune landscapes, immune checkpoint expression, and overall survival. A 12-gene risk model selected by univariate Cox and LASSO Cox regression stratified patients into high- and low-risk groups and showed modest-to-moderate predictive performance in the TCGA-LUSC, GSE30219, and GSE37745 cohorts. High-risk patients also showed higher computationally predicted IC50 values for multiple agents, suggesting lower predicted drug sensitivity rather than experimentally confirmed chemotherapy resistance. These findings indicate that COPD-associated PANoptosis genes are associated with prognosis, immune microenvironment remodeling, and predicted drug sensitivity in LUSC and may provide hypothesis-generating biomarkers for future validation.