Prognostic utility of MicroRNA-221 and interleukin-6 in cerebral ischemic stroke

Wafaa A Emam, Noha E Ibrahim, Fatma M El-Senosy, Asmaa A Elsheikh, Ahmed E Elsayed, Rasha El Attar, Sara M Elhadad, Alshaymaa M Alhabibi, Amena R Mohammed
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Abstract

Cerebral ischemic stroke has a significant mortality rate and persistent impairment. The initial diagnosis of stroke occurs by magnetic resonance imaging and computed tomography. There is a strong need for more accessible, less expensive, and non-invasive methods besides the neuroimaging methods. MicroRNAs (miRNAs) are critical regulators for ischemic stroke as they are involved in stroke pathophysiology. The goal of the current study was to determine whether microRNA-221 (miR-221) could be used as a diagnostic biomarker for patients with ischemic stroke, and whether it can serve as a promising indicator of the disease severity especially if combined with interleukin-6 (IL-6). The study included 90 subjects, 45 cerebral ischemic stroke patients and 45 controls. MiR-221 was evaluated by quantitative real-time polymerase chain reaction (q-PCR) and IL-6 by enzyme-linked immunosorbent assay (ELISA). Our study results revealed that the serum miR-221 level was significantly reduced in cerebral ischemic stroke patients when compared to the control group (p<0.0001). In addition, serum miR-221 showed a significant negative correlation with cerebral stroke severity (p<0.0001), whereas serum IL-6 showed a significant positive correlation with cerebral stroke severity (p < 0.0001). We also analyzed the receiver operator characteristic (ROC) curve and found that area under the ROC curve (AUC) for severity of ischemic stroke by miR-221 was 0.97 (95% confidence intervall0.93-1, p<0.001). Notably, the combination of serum miR-221 with IL-6 for prediction of ischemic stroke severity showed both increased sensitivity/specificity (AUC=0.99, 95% confidence interval 0.96-1, p<0.001) than miR-221 alone. We concluded that miR-221 constituted a non-invasive, sensitive, and specific biomarker that could be used for diagnosis of ischemic stroke and for prediction of its severity.
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MicroRNA-221和白细胞介素-6在缺血性脑卒中中的预后价值
缺血性脑卒中具有显著的死亡率和持续性损伤。脑卒中的初步诊断是通过磁共振成像和计算机断层扫描。除了神经成像方法之外,迫切需要更容易获得、更便宜和非侵入性的方法。MicroRNAs (miRNAs)是缺血性脑卒中的重要调控因子,参与脑卒中病理生理。本研究的目的是确定microRNA-221 (miR-221)是否可以作为缺血性卒中患者的诊断性生物标志物,以及它是否可以作为疾病严重程度的有希望的指标,特别是如果与白细胞介素-6 (IL-6)联合使用。该研究包括90名受试者,45名缺血性中风患者和45名对照组。采用实时定量聚合酶链反应(q-PCR)检测MiR-221,采用酶联免疫吸附试验(ELISA)检测IL-6。我们的研究结果显示,与对照组相比,缺血性脑卒中患者血清miR-221水平显著降低(p<0.0001)。血清miR-221与脑卒中严重程度呈显著负相关(p<0.0001),血清IL-6与脑卒中严重程度呈显著正相关(p<0.0001)。我们还分析了受试者操作特征(ROC)曲线,发现miR-221对缺血性卒中严重程度的ROC曲线下面积(AUC)为0.97(95%置信区间为0.93-1,p<0.001)。值得注意的是,血清miR-221与IL-6联合预测缺血性卒中严重程度的敏感性/特异性均高于单独使用miR-221 (AUC=0.99, 95%可信区间0.96-1,p<0.001)。我们得出结论,miR-221构成了一种无创、敏感和特异性的生物标志物,可用于缺血性卒中的诊断和预测其严重程度。
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