Integrative transcriptomic and experimental analysis identifies collagen-associated hub genes bridging chronic...

Chronic hypersensitivity pneumonitis (CHP) is an inflammatory lung disease that, upon persistent antigen exposure, progresses to fibrosis and increases the risk of lung cancer (LC). This study explores the shared molecular signatures between CHP and LC, emphasizing the role of collagen-associated genes in disease progression. Transcriptomic profiling identified 158 common differentially expressed genes, with network analysis revealing nine hub genes, COL10A1, COL22A1, COL7A1, COL5A2, COL17A1, GPR17, CCK, ADRA1A, and EDNRB, predominantly enriched in pathways related to collagen biosynthesis and extracellular matrix (ECM) organization. Significant upregulation of five collagen genes (COL10A1, COL22A1, COL7A1, COL5A2, and COL17A1) was observed, and these in silico findings were validated experimentally using bronchoalveolar lavage fluid samples from CHP (n = 7), lung cancer (n = 8), and control subjects (n = 7). Drug-gene interaction analysis identified albuterol sulfate as a potential candidate targeting collagen-related pathways. Molecular docking revealed a moderate binding affinity between albuterol sulfate and collagen, suggesting a plausible role in ECM modulation. Pharmacokinetic and ADMET analyses indicated favorable oral bioavailability (bioavailability score: 0.17) and low toxicity. In vitro validation demonstrated that albuterol sulfate (salbutamol) exhibited moderate cytotoxicity toward A549 lung cancer cells (IC₅₀ = 150 µg/mL) with markedly reduced toxicity in WI38 normal lung fibroblasts, supporting its selective anticancer activity with minimal effects on normal human cells. Overall, this study highlights the central role of collagen dysregulation in linking CHP and LC, and demonstrates how integrating in silico, in vitro, and clinical analyses, together with molecular docking approaches, can uncover novel therapeutic insights for fibrotic and oncogenic pathologies.