Abstract
Background Acute coronary syndrome (ACS) has a high incidence and mortality rate. Early detection and intervention would provide clinical benefits. This study aimed to reveal hub genes, transcription factors (TFs), and microRNAs (miRNAs) that affect plaque stability and provide the possibility for the early diagnosis and treatment of ACS. Methods We obtained gene expression matrix GSE19339 for ACS patients and healthy subjects from public database. The differentially expressed genes (DEGs) were screened using Limma package in R software. The biological functions of DEGs were shown by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Protein-protein interaction (PPI) network was mapped in Cytoscape, followed by screening of hub genes based on the Molecular Complex Detection (MCODE) plug-in. Functional Enrichment analysis tool (FunRich) and Database for Annotation, Visualization and Integrated Discovery (DAVID) were used to predict miRNAs and TFs, respectively. Finally, GSE60993 expression matrix was chosen to plot receiver operating characteristic (ROC) curves with the aim of further assessing the reliability of our findings. Results We obtained 176 DEGs and further identified 16 hub genes by MCODE. The results of functional enrichment analysis showed that DEGs mediated inflammatory response and immune-related pathways. Among the predicted miRNAs, hsa-miR-4770, hsa-miR-5195, and hsa-miR-6088 all possessed two target genes, which might be closely related to the development of ACS. Moreover, we identified 11 TFs regulating hub gene transcriptional processes. Finally, ROC curves confirmed three genes with high confidence (area under the curve > 0.9), including VEGFA, SPP1, and VCAM1. Conclusion This study suggests that three genes (VEGFA, SPP1, and VCAM1) were involved in the molecular mechanisms of ACS pathogenesis and could serve as biomarkers of disease progression.
Highlights
Acute coronary syndrome (ACS) is an acute cardiovascular event with rupture or invasion of coronary atherosclerotic plaque as pathological basis, followed by the formation of complete or incomplete occlusive thrombus, which has high morbidity and mortality in developed and developing countries [1, 2]. e fissure of atheromatous plaque causes thrombotic reaction and coronary artery blood flow obstruction, which leads to downstream myocardial ischemic damage
A total of 176 differentially expressed genes (DEGs) between ACS and control were screened out according to the above criteria, including 130 upregulated genes and 46 downregulated genes. e DEGs were visualized by volcano plot and heat map, as shown in Figures 1(a) and 1(b)
Gene function annotations of DEGs were primarily enriched in activation and migration of inflammatory cells and immune response. e top eight BP, CC, and MF terms are shown in Figure 2(a), according to the order of adjusted p value
Summary
Acute coronary syndrome (ACS) is an acute cardiovascular event with rupture or invasion of coronary atherosclerotic plaque as pathological basis, followed by the formation of complete or incomplete occlusive thrombus, which has high morbidity and mortality in developed and developing countries [1, 2]. e fissure of atheromatous plaque causes thrombotic reaction and coronary artery blood flow obstruction, which leads to downstream myocardial ischemic damage. Is study aimed to reveal hub genes, transcription factors (TFs), and microRNAs (miRNAs) that affect plaque stability and provide the possibility for the early diagnosis and treatment of ACS. Functional Enrichment analysis tool (FunRich) and Database for Annotation, Visualization and Integrated Discovery (DAVID) were used to predict miRNAs and TFs, respectively. We obtained 176 DEGs and further identified 16 hub genes by MCODE. E results of functional enrichment analysis showed that DEGs mediated inflammatory response and immune-related pathways. ROC curves confirmed three genes with high confidence (area under the curve > 0.9), including VEGFA, SPP1, and VCAM1. Is study suggests that three genes (VEGFA, SPP1, and VCAM1) were involved in the molecular mechanisms of ACS pathogenesis and could serve as biomarkers of disease progression Conclusion. is study suggests that three genes (VEGFA, SPP1, and VCAM1) were involved in the molecular mechanisms of ACS pathogenesis and could serve as biomarkers of disease progression
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