A journey to unravel the pathophysiology of stable and exacerbated Chronic Obstructive Pulmonary Disease through erythrocyte proteomics: a combined mass spectrometry/bioinformatics approach

Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disorder with high mortality. The present study explores the novel and highly enriched protein networks differentially expressed in stable and exacerbated COPD variants to elucidate the disease pathophysiology. A label-free relative quantification of erythrocyte cytosol proteome based on LC–MS/MS was performed on hemodepleted erythrocyte lysate samples of stable and exacerbated COPD with respect to healthy controls. Five highly enriched protein clusters in stable and seven in exacerbated COPD were observed, on the application of MCODE algorithm and hierarchical clustering. Functional annotation and over-representation analysis (ORA) of the differentially expressed proteins brought to light the dysregulation of molecular events such as the ERAD pathway, MAPK signaling, ciliogenesis, hypoxia, apoptosis, and neutrophil migration, resulting in the chronic inflammatory response characteristic of COPD. This study is a first-time report of the differential expression of unique proteins such as kyphoscoliosis peptidase, sperm-associated antigen-1, calpastatin, and LINE-1 in exacerbated COPD, which would lead to chronic bronchitis, bronchiectasis, and bacterial or viral infections, contributing to increased severity in exacerbated COPD. The identified proteins could serve as potential candidates for biomarkers in unraveling the pathophysiology of COPD.