Comprehensive Analysis of Immunocyte Infiltration and the Key Genes Associated with Intraplaque Hemorrhage in Carotid Atherosclerotic Plaques

Abstract

Purpose: Carotid atherosclerotic plaques are related to cerebrovascular events. We performed bioinformatics analysis to identify key biomarkers associated with intraplaque hemorrhage (IPH). Methods: We conducted a comprehensive analysis combined with DEGs, xCell, WGCNA, GSEA, and GSVA methods to identify immune infiltration cells and key genes involved in IPH by using GSE163154 from the gene expression omnibus (GEO). E-MTAB-1470 and E-MTAB-2055 from the ArrayExpress database were utilized as the validation datasets. Finally, we predicted the upstream transcription factor (TF)/miRNA and potential drugs. Results: A total of 280 genes were upregulated and 234 genes were downregulated in GSE163154. Among the upregulated pathways, the lysosome and chemokine signaling pathway were enriched, while the vascular smooth muscle (VSMC) contraction and focal adhesion were downregulated. In addition, ten coexpression modules were obtained by using the WGCNA method and two IPH and immunity-related modules were identified. In total, 454 genes overlapped by DEGs and WGCNA results were imported into Cytoscape to construct a protein–protein network. Eight genes (FCER1G, ITGB2, VAV1, CSF1R, ITGAM, TYROBP, PTK2, and PTPN11) were identified as the IPH-related gene set with area under curves (AUC) of 0.903, 0.813, and 0.829 in GSE163154, E-MTAB-2055, and E-MTAB-1470, respectively. Finally, TF/miRNA and potential drugs for these genes predicted could serve as the interventional targets. Conclusion: Immune infiltration, degradation of extracellular matrix, and suppression of focal adhesion may be implicated in the intraplaque hemorrhage and formation of prone-rupture plaques. Eight genes, identified as the IPH-related gene set, were found to be involved in IPH.