Comprehensive Analysis to Identify Key Genes Involved in Advanced Atherosclerosis

Abstract

Background. The study was aimed at finding accurate and effective therapeutic targets and deepening our understanding of the mechanisms of advanced atherosclerosis (AA). Methods. We downloaded the gene expression datasets GSE28829, GSE120521, and GSE43292 from Gene Expression Omnibus. Weighted gene coexpression network analysis (WGCNA) was performed for GSE28829, and functional enrichment analysis and protein–protein interaction network analysis were conducted on the key module. Significant genes in the key module were analyzed by molecular complex detection, and genes in the most important subnetwork were defined as hub genes. Multiple dataset analyses for hub genes were conducted. Genes that overlapped between hub genes and differentially expressed genes (DEGs) of GSE28829 and GSE120521 were defined as key genes. Further validation for key genes was performed using GSE28829 and GSE43292. Gene set enrichment analysis (GSEA) was applied to key genes. Results. A total of 77 significant genes in the key module of GSE28829 were screened out that were mainly associated with inflammation and immunity. The subnetwork was obtained from significant genes, and 18 genes in this module were defined as hub genes, which were related to immunity and expressed in multiple diseases, particularly systemic lupus erythematosus. Some hub genes were regulated by SPI1 and associated with the blood, spleen, and lung. After overlapping with DEGs of GSE28829 and GSE120521, a total of 10 genes (HCK, ITGAM, CTSS, TYROBP, LAPTM5, FCER1G, ITGB2, NCF2, AIF1, and CD86) were identified as key genes. All key genes were validated and evaluated successfully and were related to immune response pathways. Conclusion. Our study suggests that the key genes related to immune and inflammatory responses are involved in the development of AA. This may deepen our understanding of the mechanisms of and provide valuable therapeutic targets for AA.

Identification and Validation of Candidate Gene Module Along With Immune Cells Infiltration Patterns in Atherosclerosis Progression to Plaque Rupture via Transcriptome Analysis

“…Transcriptome analysis enables an expanded knowledge of complex multicellular biological systems, which has become a cornerstone of many research initiatives ( 23 , 24 ). In this study, we performed a series of bioinformatics analyses to identify the cluster gene module and immune cells infiltration patterns along with the underlying mechanistic pathways in the progression of atherosclerotic plaques.…”

Cardiovascular adverse events in chronic myeloid leukemia patients treated with nilotinib or imatinib: A systematic review, meta-analysis and integrative bioinformatics analysis

“…As a transmembrane receptor in neutrophils and monocytes/macrophages (54), TYROBP is involved in macrophage activation, lipid deposition and plaque inflammation. In the bioinformatics analysis reported by Liu et (58), TYROBP was found to be one of the key Genes Involved in Advanced Atherosclerosis. CSF1R plays an important role in the survival, proliferation and differentiation of macrophages and monocytes.…”

A comprehensive analysis of the co-pathogenesis of atrial fibrillation and atherosclerosis based on bioinformatics

“…Traditionally considered important regulators of cell survival, proliferation, adhesion, and migration [41], De cient ITGB2 could also exert a neuroprotective effect by reducing in ltrating leukocytes, which decrease in ammatory cytokines and chemokines [42]. Bioinformatics analysis showed that ITGB2 expression was up-regulated in AS patients [43][44][45]. It may be an important biomarker of bleeding in atherosclerotic plaque [46].…”

“…A variety of in ammatory pathways are driven by TYROBP [49], As a result of its involvement in the TREM-1/DAP12 pathway, TYROBP accelerates atherosclerosis progression [50]. Bioinformatics analysis showed that the expression of TYROBP was also signi cantly up-regulated in AS patients [44], It may be an important biomarker of atherosclerotic plaque bleeding [51]. Researchers found that TYROBP is a hub gene for immune response in advanced atherosclerosis, according to Chiyu Liu et al, In the treatment of advanced atherosclerotic plaque, it may be a potential interventional target [52].…”