The role of circular RNA HECTD1 expression in disease risk, disease severity, inflammation, and recurrence of acute ischemic stroke

Abstract

Background: This study aimed to explore the correlation of circular RNA HECT domain E3 ubiquitin protein ligase 1 (circRNA HECTD1) expression with disease risk, disease severity, inflammation, and recurrence of acute ischemic stroke (AIS).

Methods: A total of 160 initial AIS patients and 160 controls were enrolled in this study. Peripheral blood mononuclear cells of AIS patients and controls were separated from blood samples to detect circRNA HECTD1 expression by RT-qPCR. Inflammatory cytokines in serum of AIS patients were measured by ELISA. Furthermore, the National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate disease severity of AIS patients. Additionally, disease recurrence was documented during follow-up, and recurrence-free survival (RFS) was calculated.

Results: CircRNA HECTD1 expression was higher in AIS patients than that in controls, and the receiver operating characteristic (ROC) curve revealed that circRNA HECTD1 expression was of a good value in distinguishing AIS patients from controls with area under the curve (AUC) of 0.814 (95% CI: 0.768-0.859). In AIS patients, circRNA HECTD1 expression was positively correlated with NIHSS score, CRP, and pro-inflammatory cytokines. CircRNA HECTD1 expression was increased in AIS recurrence patients compared to non-recurrence patients, and further, ROC curve analysis disclosed that circRNA HECTD1 expression predicted higher risk of AIS recurrence (AUC: 0.694, 95% CI: 0.586-0.801). Additionally, circRNA HECTD1 expression was negatively correlated with RFS.

Conclusions: CircRNA HECTD1 expression correlates with higher disease risk, disease severity, inflammation, and recurrence of AIS.

Keywords: acute ischemic stroke; circRNA HECTD1; inflammation; recurrence; severity.

Figure 1

The relative expression of circRNA HECTD1 in AIS patients and controls. Increased circRNA HECTD1 in AIS patients compared to controls (A). Expression of circRNA HECTD1 exhibited a good value for differentiating AIS patients from controls (B). Comparison between AIS patients and controls was assessed by Wilcoxon rank sum test. P < 0.05 was considered significant. ROC curve was performed to analyze the predictive value of circRNA HECTD1 for AIS risk. CircRNA HECTD1, circular RNA HECT domain E3 ubiquitin protein ligase 1; AIS, acute ischemic stroke; AUC, area under the curve; ROC, receiver operating characteristic

Figure 2

Positive correlation between circRNA HECTD1 and NIHSS score in AIS patients. CircRNA HECTD1 expression was positively associated with NIHSS score in AIS patients. Spearman's rank correlation test was used to evaluate the association of circRNA HECTD1 with NIHSS score in AIS patients. P < 0.05 was considered significant. CircRNA HECTD1, circular RNA HECT domain E3 ubiquitin protein ligase 1; AIS, acute ischemic stroke; NIHSS, National Institutes of Health Stroke Scale

Figure 3

Expression of circRNA HECTD1 in recurrence patients and non‐recurrence patients. Recurrence patents had higher relative expression of circRNA HECTD1 than that in non‐recurrence patients (A). Expression of circRNA HECTD1 could differentiate recurrence patients and non‐recurrence patients (B). Comparison between recurrence patients and non‐recurrence patients was analyzed by Wilcoxon rank sum test. P < 0.05 was considered significant. ROC analysis was conducted to detect the ability of circRNA HECTD1 in differentiating recurrence patients from non‐recurrence patients. CircRNA HECTD1, circular RNA HECT domain E3 ubiquitin protein ligase 1; AUC, area under the curve; ROC, receiver operating characteristic

Figure 4

Negative correlation between circRNA HECTD1 expression and RFS. RFS was decreased in patients with circRNA HECTD1 high expression compared to patients with circRNA HECTD1 low expression. Kaplan‐Meier curve and log‐rank test were used to compare RFS between patients with circRNA HECTD1 high expression and patients with circRNA HECTD1 low expression. P < 0.05 was considered significant. CircRNA HECTD1, circular RNA HECT domain E3 ubiquitin protein ligase 1; RFS, recurrence‐free survival