Identification and analysis of EphrinB2/EphB4 signaling pathway and angiogenesis related biomarkers in coronary artery disease based on bioinformatics.

BACKGROUND: EphrinB2 and its receptor EphB4 have been reported to play a crucial role in the development of the cardiovascular system, and the process of coronary artery disease (CAD) is closely related to angiogenesis. The aim of this study is to identify and analyze the therapeutic value of the EphrinB2/EphB4 signaling pathway and angiogenesis-related biomarkers. METHODS: The CAD chip data (GSE42148) was used for differential analysis to identify differently expressed genes (DEGs). Key module genes associated with CAD were identified using WGCNA. Machine learning and expression validation were executed for screening biomarkers. In addition, the biological functions of biomarkers were explored using enrichment analyses. Finally, the diagnostic and therapeutic value of biomarkers was explored through immune infiltration analysis and drug prediction. RESULTS: Totally, 927 DEGs were identified in CAD and control groups. A total of 1,605 key CAD-related module genes were obtained for subsequent analyses. Then, PTX3, DLL4, and CITED4 were identified as biomarkers. Enrichment analysis suggested that three biomarkers were associated with allograft rejection. Analysis of 28 immune cell infiltrates revealed that CD56dim natural killer cell, eosinophil, mast cell, and MDSC etc. were significantly different between CAD and control groups. Finally, small-molecule drugs, notably simvastatin and calcitriol, were predicted and validated via molecular docking (binding energies < -6.0 kcal/mol) to have a potential therapeutic role in CAD by targeting PTX3 and CITED4, respectively. CONCLUSION: We obtained three EphrinB2/EphB4 signaling pathway and angiogenesis-related biomarkers (PTX3, DLL4, and CITED4) linked with CAD, which provide new references for the treatment of CAD.