Abstract
Chronic obstructive pulmonary disease (COPD) is a highly heterogeneous disease. Emphysematous phenotype is the most common and critical phenotype, which is characterized by progressive lung destruction and poor prognosis. However, the underlying mechanism of this structural damage has not been completely elucidated. A total of 12 patients with COPD emphysematous phenotype (COPD-E) and nine patients with COPD non-emphysematous phenotype (COPD-NE) were enrolled to determine differences in differential abundant protein (DAP) expression between both groups. Quantitative tandem mass tag–based proteomics was performed on lung tissue samples of all patients. A total of 29 and 15 lung tissue samples from patients in COPD-E and COPD-NE groups, respectively, were used as the validation cohort to verify the proteomic analysis results using western blotting. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted for DAPs. A total of 4,343 proteins were identified, of which 25 were upregulated and 11 were downregulated in the COPD-E group. GO and KEGG analyses showed that wound repair and retinol metabolism–related pathways play an essential role in the molecular mechanism of COPD emphysematous phenotype. Three proteins, namely, KRT17, DHRS9, and FMO3, were selected for validation. While KRT17 and DHRS9 were highly expressed in the lung tissue samples of the COPD-E group, FMO3 expression was not significantly different between both groups. In conclusion, KRT17 and DHRS9 are highly expressed in the lung tissue of patients with COPD emphysematous phenotype. Therefore, these proteins might involve in wound healing and retinol metabolism in patients with emphysematous phenotype and can be used as phenotype-specific markers.
Highlights
Chronic obstructive pulmonary disease (COPD) emphysematous phenotype is characterized by lung tissue destruction and distal airspace over inflation (Alford et al, 2010; Camp et al, 2014; Wang et al, 2018)
Functional enrichment analysis of differential abundant protein (DAP) showed that tissue repair and cell proliferation and development were primarily related to the pathogenesis of emphysematous phenotype, in addition to inflammatory response, collagen disruption, and other wellrecognized mechanisms in emphysema (Lan et al, 2019)
These results suggested that the impaired ability to repair injured tissue and lipid metabolism disorder might play an essential role in the development of prominent lung tissue destruction in COPD emphysematous phenotype
Summary
Chronic obstructive pulmonary disease (COPD) emphysematous phenotype is characterized by lung tissue destruction and distal airspace over inflation (Alford et al, 2010; Camp et al, 2014; Wang et al, 2018). Tandem mass tag (TMT) quantitative proteomics is a reliable approach to measure protein content, and it has been increasingly used to identify pathogenetic mechanisms and human disease biomarkers (Mertins et al, 2018; Dziekan et al, 2020; Wang et al, 2020). While most proteomic studies in patients with COPD have used bronchoalveolar lavage fluid (Tu et al, 2014), sputum (Titz et al, 2015), and blood (Sridhar et al, 2019), only a few have used lung tissue samples. We conducted proteomic analysis of lung tissue samples using TMT quantitative proteomic techniques to identify key molecules and their underlying mechanisms in patients with COPD emphysematous phenotype
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