Differential Expression of Serum Proteins in Chronic Obstructive Pulmonary Disease Assessed Using Label-Free Proteomics and Bioinformatics Analyses

Abstract

Purpose As a common respiratory disease, chronic obstructive pulmonary disease (COPD) has a high morbidity and mortality. Current clinical therapies are not ideal and do not improve lung function or long-term life quality. It is very important to find new potential pathogenic mechanisms, biomarkers, and targets with therapeutic value in COPD. Methods Serum samples collected from acute exacerbation and stable COPD and healthy participants were analyzed using label-free liquid chromatography tandem mass spectrometry to identify the differentially expressed proteins (DEPs) between two groups. Bioinformatics analyses were performed to determine the biological processes associated with those DEPs. Key proteins were validated by enzyme linked immunosorbent assay (ELISA). Results In total, 661 proteins were detected in serum from patients with COPD and healthy participants. Compared with healthy participants, patients with acute exacerbation of COPD had 45 DEPs, 13 were upregulated and 32 were downregulated; and patients with stable COPD had 79 DEPs, 18 were upregulated and 61 were downregulated. Gene Ontology functional annotation results indicated that the DEPs identified in patients with COPD were associated with the terms cellular anatomical entity, binding, and cellular process. Kyoto Encyclopedia of Genes and Genomes functional annotation analysis and the Clusters of Orthologous Genes database analysis indicated that the functions of these DEPs were primarily in signal transduction mechanisms and amino acid transport and metabolism. The ELISA results for three key proteins of IGFBP2, LRG1 and TAGLN were consistent with the LC-MS/MS results and the area under the receiver operating characteristic of the combined index was 0.893 (95% CI: 0.813, 0.974). Conclusion Our findings suggested pathogenic mechanisms underlying COPD stages and indicated three key proteins that may warrant further study as potential biomarkers for early diagnosis or prognosis of COPD or as therapeutic targets.

Evaluation of common protein biomarkers involved in the pathogenesis of respiratory diseases with proteomic methods: A systematic review

“…Using different samples in 119 selected studies. Accordingly, in COPD, the most commonly used selection was peripheral blood (PB); serum, plasma, or mononuclear cells were also isolated (25 of 56 studies) 42–63,114,119,123 . Also used were saliva samples in one study.…”

“…Finally, 119 studies were selected in this systematic review. Details and related findings of selected papers (age, sex, sample type, type of technique used, statistical analysis, number of increased or decreased proteins, model characteristics, validation test) are shown in supplementary files 20–123 . It listed for COPD, IPF, Asthma, BO, and mustard gas‐exposed victims, respectively.…”

“…Accordingly, in COPD, the most commonly used selection was peripheral blood (PB); serum, plasma, or mononuclear cells were also isolated (25 of 56 studies). 114,119,123 Also used were saliva samples in one study. In IPF, the most commonly used selection was Broncho-alveolar lavage fluid (BALF) (12 out of 27).…”

Impact of Lung-Related Polygenic Risk Scores on Chronic Obstructive Pulmonary Disease Risk and Their Interaction with w-3 Fatty Acid Intake in Middle-Aged and Elderly Individuals

“…The protein expressed by the PEPD gene cleaves imidodipeptides containing C-terminal proline or hydroxyproline, catalyzing collagen turnover and matrix remodeling [37]. The PEPD mutation is related to COPD [38]. Therefore, the genetic variants for COPD risk were linked to the lung structure, remodeling, and function, but not directly to oxidative stress and inflammation in the cohort.…”

The disruptive role of LRG1 on the vasculature and perivascular microenvironment

“…In addition, the damaged endothelium may disrupt vascular tone and cause dysregulation of anti-inflammatory and anti-thrombogenic endothelial properties, and together with damaged epithelium can trigger the tissue repair process ( 144 ). To date, evidence shows that LRG1 is involved in pulmonary vascular dysfunction with increased expression seen in lung disease, including chronic obstructive pulmonary disease (COPD), interstitial pneumonia, airway inflammation in asthma, and active tuberculosis, with LRG1 levels serving as a biomarker for early diagnosis, progression, and prognosis ( 38 , 66 , 145 – 148 ).…”