Peng-Fei Zheng1, Fu-Jun Liao2, Rui-Xing Yin3,4,5, Lu-Zhu Chen6, Hui Li7, Rong-Jun Nie1, Yong Wang1, Pei-Juan Liao1. 1. Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China. 2. Department of Cardiology, the First Affiliated Hospital, Guizhou Medical University, 28 Guyi Street, Guiyang, 550000, Guizhou, People's Republic of China. 3. Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China. yinruixing@163.com. 4. Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Disease Control and Prevention, 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China. yinruixing@163.com. 5. Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China. yinruixing@163.com. 6. Department of Cardiology, Shaoyang Central Hospital, 36 QianYuan lane, Shaoyang, 422000, Hunan, People's Republic of China. 7. Clinical Laboratory of The Affiliated Cancer Hospital, Guangxi Medical University, 71 Hedi Road, Nanning, 530021, Guangxi, People's Republic of China.
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.
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 ISpatients. 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 ISpatients than in normal participants and the expression levels of SOCS3, TNF and TNFAIP were higher in CAD/ISpatients 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.
Entities:
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
Authors: Aftab Alam; Hala Abubaker Bagabir; Armiya Sultan; Mohd Faizan Siddiqui; Nikhat Imam; Mustfa F Alkhanani; Ahmad Alsulimani; Shafiul Haque; Romana Ishrat Journal: Front Pharmacol Date: 2022-01-27 Impact factor: 5.810