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

Zhefan Xie; Tingting Xia; Dongxue Wu; Li Che; Wei Zhang; Xingdong Cai; Shengming Liu

doi:10.21037/atm-22-2523

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

Ann Transl Med. 2022 Jun;10(12):665. doi: 10.21037/atm-22-2523.

Authors

Zhefan Xie¹, Tingting Xia¹, Dongxue Wu¹, Li Che¹, Wei Zhang¹, Xingdong Cai¹, Shengming Liu¹

Affiliation

¹ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Abstract

Background: Chronic 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.

Methods: We 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.

Results: The 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.

Conclusions: We identified 8 hub genes of COPD based on GO, KEGG and WGCNA, which have provided insights into the pathophysiological mechanisms of COPD.

Keywords: Chronic obstructive pulmonary disease (COPD); differentially expressed genes (DEGs); hub genes; weighted gene co-expression network analysis (WGCNA).