Time-series transcriptomic analysis of cigarette smoke-associated lung responses reveals COPD-related inflammatory and epithelial remodeling modules in murine models.

Background: Cigarette smoke is the major environmental risk factor for chronic obstructive pulmonary disease (COPD), driving progressive lung inflammation and tissue injury. However, distinguishing general smoke-responsive transcriptional changes from COPD-related molecular signatures remains challenging. Methods: Public time-series transcriptomic datasets of cigarette smokeokemains challenging. and tissue injury. ity, Han-related chronic airway inflammation model (GSE132661) were analyzed. Principal component analysis (PCA), differential expression analysis, gene set enrichment analysis (GSEA), protein-protein interaction (PPI) network analysis, and functional enrichment were performed to characterize stage-dependent transcriptional dynamics. Candidate genes were further evaluated using receiver operating characteristic (ROC) analysis, quantitative real-time PCR (qPCR), and exploratory analysis in a human COPD transcriptomic dataset. Results: PCA revealed progressively increased transcriptomic divergence with prolonged smoke exposure. GSEA demonstrated a shift from early epithelial differentiation and barrier-related alterations to activation of pro-inflammatory and immune migration pathways. Six consistently upregulated genes were identified. Among them, CD177 and KRT85 showed stable expression changes across time points and models, with qPCR confirming significant upregulation after 2 and 5 months of smoke exposure ( Conclusion: This integrative time-series analysis identifies CD177 and KRT85 as murine model-derived candidate genes associated with cigarette smokeeverity confirming significant upregulation after 2 and 5 tial expression analysis, gene ance in human COPD remains exploratory, heterogeneous, and severity-dependent, and further validation in larger, clinically well-characterized cohorts is required.