Identification of differentially expressed genes and signaling pathways in chronic obstructive pulmonary disease via bioinformatic analysis

Abstract

Chronic obstructive pulmonary disease (COPD) is a multifactorial and heterogeneous disease that creates public health challenges worldwide. The underlying molecular mechanisms of COPD are not entirely clear. In this study, we aimed to identify the critical genes and potential molecular mechanisms of COPD by bioinformatic analysis. The gene expression profiles of lung tissues of COPD cases and healthy control subjects were obtained from the Gene Expression Omnibus. Differentially expressed genes were analyzed by integration with annotations from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, followed by construction of a protein‐protein interaction network and weighted gene coexpression analysis. We identified 139 differentially expressed genes associated with the progression of COPD, among which 14 Hub genes were identified and found to be enriched in certain categories, including immune and inflammatory response, response to lipopolysaccharide and receptor for advanced glycation end products binding; in addition, these Hub genes are involved in multiple signaling pathways, particularly hematopoietic cell lineage and cytokine‐cytokine receptor interaction. The 14 Hub genes were positively or negatively associated with COPD by wgcna analysis. The genes CX3CR1, PTGS2, FPR1, FPR2, S100A12, EGR1, CD163, S100A8 and S100A9 were identified to mediate inflammation and injury of the lung, and play critical roles in the pathogenesis of COPD. These findings improve our understanding of the underlying molecular mechanisms of COPD.

Identification of Common Mechanisms and Key Genes in the Chronic Obstructive Pulmonary Disease and Acute Myocardial Infarction

“…Ischemia hypoxia induces cardiomyocyte (CM) apoptosis in the process of AMI [31]. It has been reported that cytokine-cytokine receptor interaction was a signi cant pathway in COPD and AMI [24,32]. Compared with healthy controls, TNF-α level was increased in COPD patients and higher TNF-α levels were induced by illness progression [33].…”

“…Expression of S100A12 by monocytes/macrophages and neutrophils induces proin ammatory responses via ligation with the receptor for advanced glycation end-products (RAGE) and subsequent activation of intracellular signal transduction pathways [63]. S100A12 was identi ed to regulate injury and in ammation of the lung, and play key roles in the pathogenesis of COPD [24]. S100A12 activated airway epithelial cells to produce MUC5AC, which was known to contribute to severe muco-obstructive lung diseases worsening COPD pathogenesis [64,65].…”

“…S100A12 was identi ed to mediate in ammation and injury of the lung, and play critical roles in the pathogenesis of COPD [24].…”

m6A RNA methylation regulators could contribute to the occurrence of chronic obstructive pulmonary disease

“…Then, the module structure preservation was identified by module preservation R function. Finally, the gene expression profiles of each module were summarized by the module eigengene, and each module eigengene was regressed on COPD trait using the linear model in the limma R package 20 …”

“…Finally, the gene expression profiles of each module were summarized by the module eigengene, and each module eigengene was regressed on COPD trait using the linear model in the limma R package. 20 Finally, key COPD genes were acquired by taking the intersection of the overlapped DEGs and hub COPD genes.…”