Identification and verification of pivotal genes promoting the progression of atherosclerosis based on WGCNA

Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):276-285. doi: 10.1080/21691401.2023.2203185.

Abstract

As the main pathological basis for the development of cardiovascular and cerebrovascular diseases, atherosclerosis (AS) seriously affects human health. The key targets of biological information analysis of AS can help exploit therapeutic targets. The expression data of early and progressive atherosclerotic tissues were downloaded from the Gene Expression Omnibus (GEO) database. Based on GSE28829 and GSE120521, 74 key genes were obtained through differential expression analysis and weighted correlation network analysis (WGCNA) analysis, which were mainly enriched in the regulating of inflammatory response, chemokine signalling pathway, apoptosis, lipid and AS, Toll-like receptor signalling pathway and so on according to the results of the enrichment analysis. Cytoscape software was applied to screen four pivotal genes (TYROBP, ITGB2, ITGAM and TLR2) based on PPI. The results of the correlation analysis showed that the expression level of pivotal genes was positively related to macrophages M0, and was negatively related to T cells follicular helper. In addition, the expression of ITGB2 was positively related to Tregs. In this study, bioinformatics was applied to screen pivotal genes affecting the progress of AS, which were significantly related to immune-related biological functions and signal pathways of atherosclerotic tissues and the infiltration level of immune cells. Therefore, pivotal genes were expected to become therapeutic targets for AS.

Keywords: Atherosclerosis; gene set enrichment analysis; immune cell; weighted correlation network analysis.

MeSH terms

  • Apoptosis
  • Atherosclerosis* / genetics
  • Computational Biology
  • Databases, Factual
  • Gene Expression Profiling
  • Humans
  • Macrophages