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, 19 (1), 37

Genes Associated With Inflammation May Serve as Biomarkers for the Diagnosis of Coronary Artery Disease and Ischaemic Stroke

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Genes Associated With Inflammation May Serve as Biomarkers for the Diagnosis of Coronary Artery Disease and Ischaemic Stroke

Peng-Fei Zheng et al. Lipids Health Dis.

Abstract

Background: The current research aimed to expound the genes and pathways that are involved in coronary artery disease (CAD) and ischaemic stroke (IS) and the related mechanisms.

Methods: Two array CAD datasets of (GSE66360 and GSE97320) and an array IS dataset (GSE22255) were downloaded. Differentially expressed genes (DEGs) were identified using the limma package. The online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) (version 6.8; david.abcc.ncifcrf.gov) was used to annotate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses of the DEGs. A protein-protein interaction (PPI) network was constructed by Cytoscape software, and then Molecular Complex Detection (MCODE) analysis was used to screen for hub genes. The hub genes were also confirmed by RT-qPCR and unconditional logistic regression analysis in our CAD and IS patients.

Results: A total of 20 common DEGs (all upregulated) were identified between the CAD/IS and control groups. Eleven molecular functions, 3 cellular components, and 49 biological processes were confirmed by GO enrichment analysis, and the 20 common upregulated DEGs were enriched in 21 KEGG pathways. A PPI network including 24 nodes and 68 edges was constructed with the STRING online tool. After MCODE analysis, the top 5 high degree genes, including Jun proto-oncogene (JUN, degree = 9), C-X-C motif chemokine ligand 8 (CXCL8, degree = 9), tumour necrosis factor (TNF, degree = 9), suppressor of cytokine signalling 3 (SOCS3, degree = 8) and TNF alpha induced protein 3 (TNFAIP3, degree = 8) were noted. RT-qPCR results demonstrated that the expression levels of CXCL8 were increased in IS patients than in normal participants and the expression levels of SOCS3, TNF and TNFAIP were higher in CAD/IS patients than in normal participants. Meanwhile, unconditional logistic regression analysis revealed that the incidence of CAD or IS was positively correlated with the CXCL8, SOCS3, TNF and TNFAIP3.

Conclusions: The CXCL8, TNF, SOCS3 and TNFAIP3 associated with inflammation may serve as biomarkers for the diagnosis of CAD or IS. The possible mechanisms may involve the Toll-like receptor, TNF, NF-kappa B, cytokine-cytokine receptor interactions and the NOD-like receptor signalling pathways.

Keywords: Coronary artery disease; Database for annotation visualization and integrated discovery (DAVID); Gene ontology annotation; Ischaemic stroke; Kyoto encyclopedia of genes and genomes (KEGG) pathway; Protein-protein interaction (PPI) network; RT-qPCR; Unconditional logistic regression.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Venn map showing the intersection of DEGs between CAD vs normal and IS vs normal
Fig. 2
Fig. 2
Cluster heat maps of DEGs. Red represents CAD/IS group and green represents control group. a: Top 50 up-regulated DEGs between CAD and control; b: Top 27 up-regulated and 2 down- regulated DEGs between IS and control
Fig. 3
Fig. 3
Volcano plots of DEGs. Up-regulated genes are marked with red dots, and down-regulated genes are marked with green dots. a: CAD vs. control; b: IS vs. control
Fig. 4
Fig. 4
Functional annotation for DEGs. a GO enrichment analysis of DEGs; b KEGG pathways analysis of DEGs
Fig. 5
Fig. 5
PPI network construction and identification of hub genes. a PPI network of the selected DEGs. The edge shows the interaction between two genes. Significant modules identified from the PPI network using the MCODE with a score > 6.0. b Moldule-1 with MCODE = 9
Fig. 6
Fig. 6
Relative expression levels of five hub genes identified from the microarray data were verified by RT-qPCR. *P < 0.05
Fig. 7
Fig. 7
The relative risk factors for CAD and IS CAD coronary artery disease; IS ischemic stroke. *P < 0.05. **P < 0.01

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