Identification of Proteomic Signatures in Chronic Obstructive Pulmonary Disease Emphysematous Phenotype

Shuang Bai; Rui Ye; Cuihong Wang; Pengbo Sun; Di Wang; Yong Yue; Huiying Wang; Si Wu; Miao Yu; Shuhua Xi; Li Zhao

doi:10.3389/fmolb.2021.650604

Identification of Proteomic Signatures in Chronic Obstructive Pulmonary Disease Emphysematous Phenotype

Front Mol Biosci. 2021 Jul 1:8:650604. doi: 10.3389/fmolb.2021.650604. eCollection 2021.

Authors

Shuang Bai¹, Rui Ye¹, Cuihong Wang¹, Pengbo Sun¹, Di Wang¹, Yong Yue², Huiying Wang², Si Wu³, Miao Yu³, Shuhua Xi⁴, Li Zhao¹

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
² Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.
³ Department of Biobank, Shengjing Hospital of China Medical University, Shenyang, China.
⁴ Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, China.

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.

Keywords: DHRS9; KRT17; chronic obstructive pulmonary disease; emphysematous phenotype; proteomics.