Identification of novel blood biomarker panels to detect ischemic stroke in patients and their responsiveness to therapeutic intervention.
Identification of novel blood biomarker panels to detect ischemic stroke in patients and their responsiveness to therapeutic intervention.
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DOI：
10.1016/j.brainres.2018.08.012
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发表时间：
2018-11-01
期刊：
影响因子：
2.9
通讯作者：
Ford BD
中科院分区：
文献类型：
--
作者：
Augello CJ;Noll JM;Distel TJ;Wainright JD;Stout CE;Ford BD
长期以来，使用中风血液生物标志物一直被认为是确定中风发生、时间、亚型和严重程度的极好方法。在这项研究中，从缺血性中风患者中风发作后采集静脉血，并与年龄和性别匹配的对照组进行比较。我们使用由 37 种炎症分子组成的多重面板，并使用 Luminex MagPix 技术进行分析，以确定缺血性中风后血浆蛋白的变化。我们确定了中风患者血液中与对照组相比发生改变的八种关键分子。与对照组相比，中风患者血浆白介素 6 信号转导器 (sIL-6Rβ/gp130)、基质金属蛋白酶 2 (MMP-2)、骨桥蛋白、sTNF-R1 和 sTNF-R2 的水平显着升高。中风患者血浆中的干扰素-β、白细胞介素-28 和胸腺基质淋巴细胞生成素 (TSLP) 降低。患者组之间没有其他免疫学标记物存在显着差异。当中风患者接受组织纤溶酶原激活剂（t-PA）治疗时，血浆中干扰素-α2的水平显着升高，而白细胞介素-2和五聚蛋白-3的水平降低。通过接受者操作特征（ROC）分析评估分子的辨别力。根据ROC分析，区分脑卒中发生的最佳标志物是MMP-2（AUC=0.76，敏感性62.5%，特异性88.5%）、sTNF-R2（AUC=0.75，敏感性83.3%，特异性65.3%）和TSLP（AUC=0.81，敏感性66.7%，特异性96.2%）。用于评估蛋白质组合的多变量逻辑回归确定了具有高特异性和敏感性的生物标志物组（AUC = 0.96，敏感性 87.5%，特异性 96.2%）。这些结果表明了一组新型血液生物标志物，可用于识别中风患者及其对治疗干预的反应。
The use of blood biomarkers for stroke has been long considered an excellent method to determine the occurrence, timing, subtype, and severity of stroke. In this study, venous blood was obtained from ischemic stroke patients after stroke onset and compared with age and sex-matched controls. We used a multiplex panel of 37 inflammatory molecules, analyzed using Luminex MagPix technology, to identify the changes in plasma proteins after ischemic stroke. We identified eight key molecules that were altered within the blood of stroke patients as compared to controls. Plasma levels of interleukin 6 signal transducer (sIL-6Rβ/gp130), matrix metalloproteinase-2 (MMP-2), osteopontin, sTNF-R1 and sTNF-R2 were significantly higher in stroke patients compared to controls. Interferon-β, interleukin-28, and thymic stromal lymphopoietin (TSLP) were decreased in plasma from stroke patients. No other immunological markers were significantly different between patient groups. When stroke patients were treated with tissue plasminogen activator (t-PA), plasma levels of interferon-α2 significantly increased while interleukin-2 and pentraxin-3 decreased. The discriminatory power of the molecules was evaluated by receiver operating characteristic (ROC) analysis. According to ROC analysis, the best markers for distinguishing stroke occurrence were MMP-2 (AUC=0.76, sensitivity 62.5%, specificity 88.5%), sTNF-R2 (AUC=0.75, sensitivity 83.3%, specificity 65.3%) and TSLP (AUC=0.81, sensitivity 66.7%, specificity 96.2%). Multivariate logistic regression, used to evaluate the combination of proteins, identified a biomarker panel with high specificity and sensitivity (AUC=0.96, sensitivity 87.5%, specificity 96.2%). These results indicate a novel set of blood biomarkers that could be used in a panel to identify stroke patients and their responsiveness to therapeutic intervention.
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影响因子：
6.7
作者：
Nayak, Amit R.;Kashyap, Rajpal S.;Daginawala, Hatim F.
通讯作者：
Daginawala, Hatim F.
DOI：
10.1016/j.jsbmb.2016.01.006
发表时间：
2016-06
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
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作者：
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通讯作者：
Tiwari-Woodruff SK
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影响因子：
3.7
作者：
Zhang R;Pan X;Huang Z;Weber GF;Zhang G
通讯作者：
Zhang G
影响因子：
8.3
作者：
Stamova B;Xu H;Jickling G;Bushnell C;Tian Y;Ander BP;Zhan X;Liu D;Turner R;Adamczyk P;Khoury JC;Pancioli A;Jauch E;Broderick JP;Sharp FR
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