Shotgun proteomics differentiates COPD from asthma patients, smokers, and non-smoking controls: a pilot exploratory study

A biomarker panel that improves chronic obstructive pulmonary disease (COPD) diagnosis, even in the presence of confounding factors such as asthma and smoking, is of great importance. Label-free proteomic analysis was conducted in four groups (10 subjects each): COPD patients, asthma patients, smoker controls, and non-smoker controls. A total of 1469 proteins were identified in the 40 serum samples, of which 29 were differentially abundant in the COPD group ( p < 0.05 and > 2.0-fold change) compared with asthma and control groups. Five differentially abundant proteins (DAPs) stood out in volcano plots and heatmaps: ubiquitin carboxyl-terminal hydrolase 31 (USP31), RING finger protein 10 (RNF10) and transforming acidic coiled-coil containing protein 2 (TACC2) differentiated COPD from both control groups and asthma patients, while mitogen-activated protein 3-kinase 10 (MAP3K10) and collagen type V alpha 1 chain (COL5A1) differentiated COPD from healthy controls. Logistic regression models with five-fold cross-validation, based on this protein set, achieved over 80% accuracy in diagnosing COPD. DAPs were explored for pathway enrichment using Reactome and PANTHER, revealing pathways related to COPD pathophysiology. Knowledge of these alterations is important for identifying novel biomarkers to aid diagnosis and therapeutic strategies, contributing to precision medicine in COPD.