Abstract
This investigation seeks to dissect coronary artery disease molecular target candidates along with its underlying molecular mechanisms. Data on patients with CAD across three separate array data sets, GSE66360, GSE19339 and GSE97320 were extracted. The gene expression profiles were obtained by normalizing and removing the differences between the three data sets, and important modules linked to coronary heart disease were identified using weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and genomes (KEGG) pathway enrichment analyses were applied in order to identify statistically significant genetic modules with the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool (version 6.8; http://david.abcc.ncifcrf.gov). The online STRING tool was used to construct a protein–protein interaction (PPI) network, followed by the use of Molecular Complex Detection (MCODE) plug-ins in Cytoscape software to identify hub genes. Two significant modules (green-yellow and magenta) were identified in the CAD samples. Genes in the magenta module were noted to be involved in inflammatory and immune-related pathways, based on GO and KEGG enrichment analyses. After the MCODE analysis, two different MCODE complexes were identified in the magenta module, and four hub genes (ITGAM, degree = 39; CAMP, degree = 37; TYROBP, degree = 28; ICAM1, degree = 18) were uncovered to be critical players in mediating CAD. Independent verification data as well as our RT-qPCR results were highly consistent with the above finding. ITGAM, CAMP, TYROBP and ICAM1 are potential targets in CAD. The underlying mechanism may be related to the transendothelial migration of leukocytes and the immune response.
Highlights
This investigation seeks to dissect coronary artery disease molecular target candidates along with its underlying molecular mechanisms
From coronary artery disease (CAD) patients (GSE66360, GSE19339 and GSE97320) in order to carry out weighted gene co-expression network analysis (WGCNA) analysis, which subsequently identified 2 modules that were significantly correlated with CAD
Four hub genes (ITGAM, TYROBP, Intercellular adhesion molecule 1 (ICAM1) and CAMP) were identified in two moleculars that were detected by Molecular Complex Detection (MCODE) by analyzing the protein–protein interaction (PPI) protein interaction network
Summary
This investigation seeks to dissect coronary artery disease molecular target candidates along with its underlying molecular mechanisms. The gene expression profiles were obtained by normalizing and removing the differences between the three data sets, and important modules linked to coronary heart disease were identified using weighted gene co-expression network analysis (WGCNA). After the MCODE analysis, two different MCODE complexes were identified in the magenta module, and four hub genes (ITGAM, degree = 39; CAMP, degree = 37; TYROBP, degree = 28; ICAM1, degree = 18) were uncovered to be critical players in mediating CAD. Inflammation plays a crucial role in the pathophysiology of coronary artery disease (CAD), it is involved in the formation, erosion and final rupture of atherosclerotic plaque, resulting in partial or total occlusion of coronary artery This might result in myocardial ischemia and hypoxia and thereby an acute myocardial infarction (AMI)[1]. Given the capabilities of WGCNA in formulating a co-expression network comprising of significant modules, we are able to glean new information regarding CAD features and may uncover novel insights in CAD-related molecular mechanisms, signaling pathways and genetic biomarkers
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