Introduction

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease and is among the top three diseases in the world with respect to morbidity and mortality. Despite some advancements in treatment and understanding of the disease process in COPD, knowledge remains limited. This directed our attention towards exploring the gene expression profile of COPD patients to identify novel target genes that can help develop new therapies.

Methods
Bronchial biopsies of non-smoking healthy (n=18), ex- and current-smoking COPD (n=56) patients with varying degrees of severity were collected, and bulk RNA sequencing was performed. Differential gene expression analysis was assessed using the edgeR package. We performed cellular-type deconvolution analysis on the different cell types of the airway epithelium using CIBERSORT method and removed any influence of cellular heterogeneity. Moreover, master regulators (MRs) driving COPD pathogenesis were identified using ARACNE and Viper packages in R.

Results

We have performed genome-wide transcriptomic analysis of COPD patients relative to healthy individuals. We have initially identified 167 differentially expressed genes, of which 34, including AKR1B10,IRX4,CA12, LCN10 and TMIGD3 (logFC>1,FDR<0.05), were identified post-cellular composition correction, increasing confidence that they are associated with COPD. In addition, we identified several MRs, including ESRRA, TIGD5 and MXD3 (Differential activity>6.5, FDR< 0.01), involved in COPD progression.

Conclusion

Our study reveals several novel candidate genes that might be involved in COPD development.