Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p

Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p
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DOI:
10.1159/000488365
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发表时间:
2018-01-01
影响因子:
2.9
通讯作者:
Liu, Jing-Li
Liu, Jing-Li
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Wei;Li, Dong-Bin;Liu, Jing-Li

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背景:缺血性中风(IS)的早期和准确诊断需要使用优化的生物标志物。外体microRNAs由于其稳定性和特异性,具有作为生物标志物的潜力。我们研究了血浆来源的外体microRNA-21-5p和microRNA-30a-5p在IS不同阶段的表达水平。方法:143例IS患者和24例非卒中对照组入选。将患者分为5组:1组为超急性期IS(HIS,6h内),2组为急性期IS(AIS,第1~3天,第4~7天),1组为亚急性期IS(SIS,第8~14天),1组为恢复期IS(RIS,Days&Gt;14天)。使用QIAGEN exoRNasy试剂盒分离血浆外切体,并通过透射电子显微镜、纳米颗粒跟踪和流式细胞术进行检查。实时定量聚合酶链式反应检测miRNA-21-5p和miRNA-30a-5p的表达水平。结果:SIS和RIS患者血浆外体miR-21-5p水平均显著高于对照组(P<0.05和P<0.01)。HIS组miR-30a-5p水平显著高于对照组(P<0.05),AIS组(第1~3天)显著低于对照组(P<0.05)。AIS组(第1~3天)与His组相比,两种miRNA的表达均减少(p分别为0.053和0.001)。MiR-21-5p的曲线下面积分别为0.714(95%CI 0.570~0.859,p=0.007)和0.734(95%CI 0.596~0.871,p=0.003),MIR-30a-5p的曲线下面积分别为0.826(95%CI 0.665~0.988,p=0.001)和0.438(第1~3天;95%CI 0.240~0.635,p=0.516)。结论:血浆来源的胞外体miR-21-5p和miRNA-30a-5p联合检测对IS的诊断和His、SIS、RIS的鉴别诊断具有较好的应用前景,尤其是miRNA-30a-5p对His期的诊断具有较好的应用前景。我们的结果为临床医生在早期诊断中的应用提供了新的参考,并确定了生物标志物在溶栓治疗中的可能价值。(C)2018年S.Karger AG,巴塞尔
Background: Early and accurate diagnosis of ischaemic stroke (IS) requires the use of an optimized biomarker. Exosomal microRNAs have the potential to serve as biomarkers owing to their stability and specificity. We investigated the expression levels of plasma-derived exosomal microRNA-21-5p and microRNA-30a-5p in the different phases of IS. Methods: One hundred forty-three patients with IS and 24 non-stroke controls were enrolled. The patients were divided into the following 5 groups: 1 group for the hyperacute phase IS (HIS, within 6 h); two for the acute phase IS (AIS, including days 1-3 and days 4-7); one for the subacute phase IS (SIS, days 8-14); and one for the recovery phase IS (RIS, days >14). Plasma exosomes were isolated using a QIAGEN exoRNeasy kit and examined by transmission electron microscopy, nanoparticle tracking, and flow cytometry. The expression levels of miRNA-21-5p and miRNA-30a-5p were detected by quantitative real-time polymerase chain reaction. Results: The plasma exosomal miR-21-5p levels in SIS and RIS were significantly higher than that in controls (p < 0.05 and p < 0.01 respectively). The levels of miR-30a-5p in HIS were significantly higher (p < 0.05) and in AIS (days 1-3) were lower than that in controls (p < 0.05). In AIS (days 1-3), both miRNAs were decreased compared with the HIS group (p = 0.053 and 0.001, respectively). The area under the curve (AUC) of the miR-21-5p was 0.714 for SIS (95% CI 0.570-0.859, p = 0.007), 0.734 for RIS (95% CI 0.596-0.871, p = 0.003); the AUC of the miR-30a-5p was 0.826 for HIS (95% CI 0.665-0.988, p = 0.001), 0.438 for AIS (days 1-3; 95% CI 0.240-0.635, p = 0.516). Conclusions: The plasma-derived exosomal miR-21-5p and miRNA-30a-5p in combination are promising biomarkers for diagnosing IS and distinguishing among HIS, SIS, and RIS, especially miRNA-30a-5p for the diagnosis of the HIS phase. Our results provide a new reference for clinicians to apply in early-stage diagnosis and identifies the possible value of biomarkers for IS thrombolysis therapy. (C) 2018 S. Karger AG, Basel