Identification of the key genes in chronic obstructive pulmonary disease by weighted gene co-expression network analysis.

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is prevalent mainly in older adults, especially those who are smokers. It appears to be regulated by multiple genes, but there is some degree of familial clustering. The evidence to date suggests that COPD-associated biomarkers are largely inadequate for disease diagnosis, so we conducted a comprehensive search for more specific genetic markers.MethodsWe used 3 datasets from the Gene Expression Omnibus (GEO) database. By investigating the biological information [i.e., Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and weighted gene co-expression network analysis (WGCNA)], we filtered out 8 differentially expressed genes (DEGs) and validated the transcript levels of those hub genes in 16HBE cell lines, THP-1 cell lines and lung tissue of COPD patients.ResultsThe 8 hub genes comprised amyloid precursor protein (APP), fibronectin 1, insulin-like growth factor 1 (IGF1), β-actin, capping actin protein of muscle Z-line subunit alpha 2, secreted phosphoprotein 1 (SPP1), catalase (CAT), and colony stimulating factor 2 (CSF2) were selected from among the DEGs. Cigarette smoke extract-stimulated 16HBE cells were found to highly express SPP1, CSF2, and IGF1. In addition, IGF1 levels were increased and IGF1 and APP levels were decreased in CSE-stimulated THP-1 cells. SPP1 and FN1 showed increased expression levels in lung tissue of COPD patients, but the opposite held for APP and CAT.ConclusionsWe identified 8 hub genes of COPD based on GO, KEGG and WGCNA, which have provided insights into the pathophysiological mechanisms of COPD.