Elucidating the Prognostic Biomarkers and Immune Correlations in the Co- occurrence of Chronic Obstructive Pulmonary Disease and Lung Squamous Cell Carcinoma

Abstract Background: Chronic obstructive pulmonary disease (COPD) elevated the risk of lung squamous cell carcinoma (LUSC), but the underlying molecular links and their effects on disease progression were unclear. Methods: This study performed a comprehensive analysis of microarray and RNA-Seq data from six independent cohorts to identify key differentially expressed genes (DEGs) between COPD and LUSC patients. It conducted survival analysis using the TCGA-LUSC dataset and constructed a risk prediction model for the identified DEGs through LASSO regression, accounting for smoking history in LUSC-TCGA patients. The immune correlations and tumor immunophenotype profiling of the risk model were further analyzed. Results: Distinct gene expression profiles were identified in patients with both COPD and LUSC compared to those with either condition alone, with seven genes showing significant dysregulation. This suggested a unique molecular signature for combined disease pathology. PTPN3 and ADH1C were pinpointed as potential prognostic biomarkers using a LASSO model. These genes also demonstrated negative correlations with various immune cells and positive correlations with tumor-promoting processes. Conclusion: This study reveals the molecular connection between COPD and LUSC, pinpointing biomarkers for disease evolution and therapeutic response, and emphasizes the intricate treatment dynamics due to COPD's genetic and immune influences on LUSC prognosis