Related Experiment Video
Updated: Apr 27, 2026
Author Spotlight: Integrated Multi-Omics Analysis for Unveiling Multicellular Immune Signatures in Clinical Heart Attack Cohorts
Published on: September 20, 2024
Identification of key genes and crucial modules associated with coronary artery disease by bioinformatics analysis
Xuemei Zhang1, Xiaoshu Cheng2, Huifeng Liu3
1Department of Cardiology, Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.
Insights
This study identified GRB2 and HSPA8 genes and chemokine/focal adhesion pathways as key players in coronary artery disease (CAD) development, offering potential targets for future research and treatment strategies.
Area of Science:
- Genomics and Bioinformatics
- Cardiovascular Research
- Molecular Biology
Background:
- Coronary artery disease (CAD) is a leading cause of mortality worldwide.
- Identifying key genetic factors and molecular pathways involved in CAD is crucial for developing effective treatments.
- Previous studies have explored genetic associations, but a comprehensive network-based analysis is needed.
Purpose of the Study:
- To identify key differentially expressed genes (DEGs) associated with CAD.
- To explore the protein-protein interaction (PPI) networks and signaling pathways involved in CAD pathogenesis.
- To pinpoint crucial genes and pathways that may serve as therapeutic targets for CAD.
Main Methods:
- Downloaded and analyzed gene expression profiles from the Gene Expression Omnibus (GEO) database (GSE12288).
- Identified DEGs using t-tests and constructed PPI networks using STRING.
- Utilized DAVID for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.
- Identified crucial modules and analyzed topological properties using Cytoscape plugins (jActiveModule, NetworkAnalyzer).
Main Results:
- Identified 151, 362, and 425 DEGs in CAD grades I, II, and III, respectively.
- The gene GRB2 was the only common DEG across all three grades.
- Identified 10 crucial modules in PPI networks, with 4 significantly enriched for GO biological processes.
- GRB2 and HSPA8 were identified as key nodes with high betweenness centrality.
- Chemokine and focal adhesion signaling pathways were found to be relatively abundant in CAD.
Conclusions:
- GRB2 and HSPA8 proteins are potentially critical in CAD development.
- Chemokine and focal adhesion signaling pathways are significantly associated with CAD.
- These findings provide novel insights into CAD pathogenesis and suggest potential therapeutic targets.
Abstract:
The aim of this study was to identify key genes associated with coronary artery disease (CAD) and to explore the related signaling pathways. Gene expression profiles of 110 CAD and 112 non-CAD, healthy patients [CAD index (CADi) >23 and =0, respectively] were downloaded from the Gene Expression Omnibus (GEO) database (accession: GSE12288). The differentially expressed genes (DEGs) in CAD were identified using t-tests, and protein-protein interaction (PPI) networks for these DEGs were constructed using the Search Tool for the Retrieval of InteractiNg Genes (STRING) database. The Database for Annotation, Visualization and Integrated Discovery (DAVID) tool was used to identify potentially enriched biological processes (BP) among the DEGs using Gene Ontology (GO) terms, and to identify the related pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. In addition, expression-activated subnetworks (crucial modules) of the constructed PPI networks were identified using the jActiveModule plug-in, and their topological properties were analyzed using NetworkAnalyzer, both available from Cytoscape. The patient specimens were classified as grade I, II and III based on CADi values. There were 151 DEGs in grade I, 362 in grade II and 425 in grade III. In the PPI network, the gene GRB2, encoding the growth factor receptor-bound protein 2, was the only common DEG among the three grades. In addition, 10 crucial modules were identified in the PPIs, 4 of which showed significant enrichment for GO BP terms. In the 12 nodes with the highest betweenness centrality, we found two genes, encoding GRB2 and the heat shock 70 kDa protein 8 (HSPA8). Moreover, the chemokine and focal adhesion signaling pathways were selected based on their relative abundance in CAD. The GRB2 and HSPA8 proteins, as well as the chemokine and focal adhension signaling pathways, might therefore be critical for the development of CAD.
Related Concept Videos
01:30Coronary Artery Disease I: Introduction
01:29Pharmacogenomics: Identification of New Drug Targets
01:26Coronary Artery Disease II: Pathophysiology
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...