Identification of Novel Hub Genes in Atherosclerosis Induced by Abnormal Endothelial Shear Stress via Bioinformatics Analysis

Abstract Background: Abnormal endothelial shear stress (ESS) is a significant risk factor for atherosclerosis (AS); however, the genes and pathways between ESS and AS are poorly understood. Here, we screened hub genes and potential regulatory targets linked to the progression of AS induced by abnormal ESS. Methods: GSE45225, GSE23289 and GSE43292 were downloaded from the Gene Expression Omnibus (GEO) database. The limma package in R was used to identify differentially expressed genes (DEGs). The common DEGs of GSE45225 and GSE43292 were regarded as low-ESS-AS related genes. Co-DEGs obtained from GSE23289 and GSE43292 were considered as high-ESS-AS related genes. Next, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted. Molecular interaction networks were assembled and their crucial genes were identified using Cytoscape. Our findings were also verified in GSE28829, GSE100927. Results: A total of 85 low-ESS-AS related genes and 118 high-ESS-AS related genes were identified. FBXO32, ICAM1 and TNFRSF1B were identified as key hub genes and validated in the GSE28829, GSE100927. ROC analysis indicates that FBXO32 (AUC=0.782), ICAM1 (AUC=0.822) and TNFRSF1B (AUC=0.801) could effectively distinguish the atherosclerotic plaque and normal arterial. Conclusion: We identified ICAM1, TNFRSF1B and FBXO32 as key genes associated with abnormal ESS and AS and may provide potential prevention and treatment target of AS induced by abnormal ESS.