Differential coexpression networks in bronchiolitis and emphysema phenotypes reveal heterogeneous mechanisms of chronic obstructive pulmonary disease

• Published in: Journal of cellular and molecular medicine Vol. 23; no. 10; pp. 6989 - 6999
• Main Authors: Qin, Jiangyue, Yang, Ting, Zeng, Ni, Wan, Chun, Gao, Lijuan, Li, Xiaoou, Chen, Lei, Shen, Yongchun, Wen, Fuqiang
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.10.2019; John Wiley and Sons Inc
• Subjects: Apoptosis; Biomarkers; bronchiolitis; Bronchiolitis - genetics; Bronchopneumonia; Chronic obstructive pulmonary disease; Cluster Analysis; Data collection; Datasets; Degranulation; differential coexpression; DNA microarrays; Dyspnea; Emphysema; Emphysema - genetics; Encyclopedias; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Gene Regulatory Networks; Genes; Genomes; Humans; Lung diseases; Mitochondria; Molecular modelling; Molecular Sequence Annotation; Obstructive lung disease; Original; Phenotype; Phenotypes; Proteolysis; Pulmonary Disease, Chronic Obstructive - genetics; Rho protein; Signal transduction; Signal Transduction - genetics; Stromelysin 2; Studies; Therapeutic applications; Transduction; China; phenotype; differential coexpression; bronchiolitis; chronic obstructive pulmonary disease; emphysema
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.14585

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with multiple molecular mechanisms. To investigate and contrast the molecular processes differing between bronchiolitis and emphysema phenotypes of COPD, we downloaded the GSE69818 microarray data set from the Gene Expression Omnibus (GEO), which based on lung tissues from 38 patients with emphysema and 32 patients with bronchiolitis. Then, weighted gene coexpression network analysis (WGCNA) and differential coexpression (DiffCoEx) analysis were performed, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis (KEGG) analysis. Modules and hub genes for bronchiolitis and emphysema were identified, and we found that genes in modules linked to neutrophil degranulation, Rho protein signal transduction and B cell receptor signalling were coexpressed in emphysema. DiffCoEx analysis showed that four hub genes (IFT88, CCDC103, MMP10 and Bik) were consistently expressed in emphysema patients; these hub genes were enriched, respectively, for functions of cilium assembly and movement, proteolysis and apoptotic mitochondrial changes. In our re‐analysis of GSE69818, gene expression networks in relation to emphysema deepen insights into the molecular mechanism of COPD and also identify some promising therapeutic targets.