Researchers Uncover Differentially Expressed Genes Linked With Development, Progression of COPD

In study findings demonstrating differentially expressed genes (DEGs) among healthy patients and those with chronic obstructive pulmonary disease (COPD), researchers show that key genes CYP1B1, VEGFA, BCL2, and CDKN1A may have significance in analyzing the development and progression of COPD.

Published in the International Journal of Chronic Obstructive Pulmonary Disease, the study authors sought to explore the mechanisms involved in the development of COPD. Several analyses have highlighted the significant differences in gene expressions exhibited by patients with COPD, indicating the potential role of DEGs as an underlying cause in the development and progression of the disease.

The researchers derived information from the Gene Expression Omnibus database on a micro RNA expression profile GSE100281, containing 79 COPD and 16 healthy samples. The DEGs between the COPD and healthy samples were analyzed using the limma package, with a functional enrichment analysis additionally carried out using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool.

The DEG-compound pairs were then predicted using the Comparative Toxicogenomics Database. The study authors constructed a metabolite network prediction through the MetaboAnalyst pipeline, where Kyoto Encyclopedia of Genes and Genomes metabolite IDs corresponding to the compounds were obtained. The expression of key genes was ultimately determined using quantitative polymerase chain reaction (qPCR).

The researchers screened and functionally analyzed 594 DEGs between the COPD and healthy samples, consisting of 242 upregulated and 352 downregulated genes. Analyses exhibited 696 DEG-compound pairs, including CYP1B1, VEGFA, BCL2, and CDKN1A, and 57 metabolites. BCL2 was found to be significantly associated with C00469 (ethanol) and C00389 (quercetin), pairs that were additionally associated with hsa04750 (inflammatory mediator regulation of TRP channels) in the gene-metabolite network.

CYP1B1, VEGFA, BCL2, and CDKN1A were all included in the top 10 DEG-compound pairs and shown to be consistent with that predicted using bioinformatic analysis in the qPCR results.

“The key genes CYP1B1, VEGFA, BCL2, and CDKN1A may affect the mechanisms underlying the development and progression of COPD. Specifically, BCL2 may be involved in the development of COPD via inflammation-mediated regulation of TRP [transient receptor potential] channels and AMPK [AMP-activated protein kinase] signaling pathway,” said the study authors.

They noted that further in-depth experimental studies are warranted to confirm results.

Reference

Yang D, Yan Y, Hu F, et al. CYP1B1, VEGFA, BCL2, and CDKN1A affect the development of chronic obstructive pulmonary disease [published online January 23, 2020]. Int J Chron Obstruct Pulmon Dis. doi: 10.2147/COPD.S220675.