Circular RNA FUNDC1 for Prediction of Acute Phase Outcome and Long-Term Survival of Acute Ischemic Stroke

Front Neurol. 2022 Jun 3:13:846198. doi: 10.3389/fneur.2022.846198. eCollection 2022.

Abstract

Circular RNAs (CircRNAs) have shown promising potential in the diagnosis and the prediction of outcomes of stroke. This study aimed to explore the potential value of circRNAs for identifying acute neurological deterioration and estimating long-term survival for acute ischemic stroke (AIS). One hundred healthy controls and 200 patients with AIS within 72 h were recruited, 140 of whom were admitted within 24 h after onset. CircRNA levels in peripheral blood were measured by quantitative polymerase chain reaction (qPCR). Compared to the controls, the levels of three circRNAs were significantly increased in three subgroups of patients, including large artery atherosclerosis (LAA) stroke, small artery occlusion (SAO) stroke, and cardioembolism (CE) stroke (all P < 0.001). Among, LAA stroke patients had higher levels of circular RNA FUNDC1 (circFUNDC1) compared to SAO stroke patients (P = 0.015). CircFUNDC1 levels were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores on the 7th day only in LAA patients (P = 0.048, r = 0.226). It should be noted that the levels of circFUNDC1 in patients with early neurological deterioration (END), admitted within 24 h after onset, were significantly higher than those without END (P = 0.013). In addition, circFUNDC1 levels positively correlated with baseline NIHSS scores (P = 0.016, r = 0.203) or the 7th day NIHSS scores (P = 0.001, r = 0.289) in patients within 24 h after onset. Importantly, after 18 months of follow-up, a significant difference was observed on survival Kaplan-Meier curves (P = 0.042) between AIS patients with low (below cut-off) or high circFUNDC1 levels (above cut-off). Circulating circFUNDC1 could be a potential biomarker for predicting acute-phase outcome and long-term survival in AIS.

Keywords: acute ischemic stroke; biomarker; circular RNA; early neurological deterioration; outcome.