Abstract
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.
Highlights
Chronic obstructive pulmonary disease (COPD) affects millions of people all over the world, and it is associated with high morbidity and mortality.[1]
This suggests that the bronchiolitis and em‐ physema phenotypes of COPD occur via different mechanisms, leading to different treatment response and clinical outcome
The present study identified coexpression of several B cell–related genes enriched in the tan module, which positively correlate with em‐ physema, which is consistent with the work of Faner et al[15] and other groups that implicates antigen and immune processes in COPD patho‐ genesis.[25,26]
Summary
Chronic obstructive pulmonary disease (COPD) affects millions of people all over the world, and it is associated with high morbidity and mortality.[1]. The two classical clinical phenotypes of COPD are bronchiol‐ itis and emphysema.[4] Patients with bronchiolitis display persistent inflammation, goblet cell hyperplasia and mucin hyperexpression in the airway,[5] increasing intraluminal mucus, wall muscle fibrosis and airway stenosis.[6] Emphysema involves elastolytic destruction of the alveolar wall without obvious fibrosis and loss of normal lung tissue.[7] COPD patients with either the bronchiolitis or the emphysema phenotype differ in their clinical characteristics and treatment response. Weighted gene coexpression network analysis (WGCNA) identifies correlations among genes across mi‐ croarray samples, so it can detect clusters (modules) of highly cor‐ related genes. Using differential gene expression analysis, Faner et al[15] charac‐ terized genes differentially expressed between COPD patients with bronchiolitis or emphysema They found that several B cell–related genes were up‐regulated in patients with emphysema but not in pa‐ tients with bronchiolitis. Our aim was to begin to identify genes differentially coexpressed between the bronchiolitis and em‐ physema phenotypes of COPD as a way to develop promising bio‐ markers for diagnosis and as a way to identify molecular pathways involved in each phenotype
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