Background: Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable airway disease. This study aimed to identify key genes related to COPD pathogenesis through an integrated transcriptomic and proteomic analysis of lung tissue from COPD subjects undergoing lung resection for malignancy.

Methods: We performed RNA sequencing, gene expression analysis, and gene set enrichment analysis (GSEA) on lung tissue in 13 non-smokers, 16 smokers, and 16 COPD patients. Key genes were verified by RT-qPCR, immunohistochemistry and Western blot in human lung tissues, cigarette smoke extract (CSE)-exposed human bronchial epithelial cell line (BEAS-2B cells), and a cigarette smoke (CS)-induced mouse model.

Results: There were 521 differentially expressed genes between non-smokers and smokers, 57 genes between smokers and COPD patients, and 860 genes between non-smokers and COPD patients. Fibrinogen gamma chain (FGG) was highly expressed in COPD patients versus smokers and in COPD patients versus healthy controls. GSEA of the COPD patients with the highest FGG expression were enriched in the B cell receptor signaling pathway, pantothenate and CoA biosynthesis, Fc epsilon RI signaling pathway, and the Toll-like receptor (TLR) signaling pathway. RT-PCR analysis confirmed enhanced FGG mRNA levels in the lungs of both smokers and COPD patients compared to non-smokers and in CSE-exposed cells compared to control cells. FGG protein levels were elevated in the lungs of COPD patients and smokers compared to non-smokers and in the lungs of CS-exposed mice compared to control mice.

Conclusions: FGG may serve as a biomarker for COPD and may play an important role in its pathogenesis.