Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes
Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes
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DOI：
10.1080/20013078.2020.1713540
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发表时间：
2020-01-01
影响因子：
16
通讯作者：
Van Keuren-Jensen, Kendall
中科院分区：
文献类型：
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作者：
Kalani, M. Yashar S.;Alsop, Eric;Van Keuren-Jensen, Kendall
快速识别患有脑缺血的患者，同时排除脑出血，可以帮助患者分诊，并扩大患者获得化学和机械血运重建术的机会。我们利用来自自发性肺内出血（IPH）、动脉瘤性蛛网膜下腔出血（SAH）和脑血管闭塞引起的缺血性中风患者的临床样本，试图鉴定与主要中风亚型相关的细胞外小泡的血基细胞外microRNAs 15（前mirnas）。我们采集了IPH （n = 19）、SAH （n = 17）和缺血性脑卒中（n = 21）患者的血液。我们从血浆中分离细胞外囊泡，提取RNA货物，对小RNA进行测序，并进行生物信息学分析，以确定预测中风亚型的前mirna生物标志物。67种mirna在卒中亚型中存在显著差异。出血性卒中和缺血性卒中的exmirna亚群不同，LASSO分析可以区分SAH与其他亚型，准确率为0.972 +/- 0.002。进一步分析预测，25种miRNA分类器将IPH与缺血性脑卒中区分开来的准确率为0.811 +/- 0.004，将出血与缺血性脑卒中区分开来的准确率为0.813 +/- 0.003。基于血液的前mirna具有预测价值，并且可以通过改进和验证来区分主要的中风亚型。这样的生物标记物有一天可以帮助患者进行分类，扩大有资格接受有效治疗的人群。
Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 +/- 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 +/- 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 +/- 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.