Integrative analysis of senescence-related genes in endothelial cells of Cerebral Ischemic Stroke patients

Abstract Growing evidence points that aging is a predominant risk factor for Cerebral Ischemic Stroke (CIS), caused by endothelial cells dysfunction and senescence. Our research was aimed to explore potential vital cellar senescence-related differentially expressed genes (CSRDEGs) as diagnostic biomarkers for CIS by bioinformatic analysis. We acquired 8058 DRGs from the combined dataset(GSE22255 and GSE58294, and filtered 377 CSRGs from the GeneCards database and existing literature. 147 CSRDEGs were chosen from intersecting DRGs and CSRGs, and 15 core genes were obtained via LASSO regression and SVM analysis combined, consisting of 4 senescence inhibitor genes and 10 senescence promoter genes. There were 6 CSRDEGs expression levels (EWSR1, HJURP, SMARCA4, GKN1, MAP2K6, NEK1) could distinguish the high or low CSs. Association between 15 core genes and immune cell infiltration revealed that BLK positively correlated with naive B cells, while KAT5 inversely correlated with memory quiescent CD4+ T cells. Furthermore, through constructed a Logistic regression model and identified the model efficacity by various methods. Which suggested that 3 model genes (CSNK2A1, HJURP, MAP2K6) had a great diagnostic efficacy in CIS patients. AUC of ROC was 0.876 (95%CI 0.815–0.937). Finally, we found 23 miRNA molecules and 64 transcription factors (TFs) associated with 3 model genes. In summary, CSNK2A1, HJURP, MAP2K6 have potential opportunity to be as diagnostic markers of CIS at early stage.