Stroke has a high incidence rate and often leads to permanent disability, particularly if it is not treated promptly. However, no blood biomarkers for early diagnosis are available to date. Therefore, we sought to detect stroke-specific blood biomarkers by identifying proteins associated with the underlying coagulation mechanism, which accounts for more than 80% of all stroke cases. Protein profiling was performed using blood samples from 16 healthy controls and 18 patients who suffered a stroke as the discovery set. We identified upregulated proteins (> 1.5-fold change and p value < 0.05) in patients who suffered a stroke relative to the corresponding levels in healthy controls by nano-liquid chromatography-tandem mass spectrometry using data-independent acquisition based on sequential window acquisition of all theoretical mass spectra, which was developed to improve the consistency and accuracy of candidate proteins. Pathway analysis confirmed that the upregulated proteins were mainly involved in blood coagulation. Among these, we selected prothrombin, plasminogen, fibrinogen alpha-chain, and histidine-rich glycoprotein as candidate biomarkers. Multiple reaction monitoring analysis was performed on a validation set of 61 serum samples (31 healthy controls and 30 stroke patients) to assess the diagnostic value of the candidate biomarkers. All four proteins showed higher expression levels in patients with stroke than in healthy controls. The areas under the receiver operating characteristic curve were greater than 0.9, confirming their clinical value. These four blood coagulation proteins may help in diagnosing stroke more accurately and quickly.

中文翻译：

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蛋白质组学揭示了与凝血级联相关的缺血性卒中的血浆生物标志物。

中风的发病率很高，经常导致永久性残疾，尤其是如果不及时治疗的话。但是，迄今为止尚无用于早期诊断的血液生物标志物。因此，我们试图通过鉴定与潜在的凝血机制相关的蛋白质来检测卒中特异性血液生物标志物，该蛋白质占所有卒中病例的80％以上。使用来自16名健康对照者和18名中风的患者的血样作为发现集进行了蛋白质分析。我们鉴定出上调的蛋白质（> 1.5倍变化和p值小于0.05），通过基于所有理论质谱的连续窗口采集的数据独立采集的纳米液相色谱-串联质谱法通过纳米液相色谱-串联质谱法对健康对照组中相对应水平的卒中患者进行了研究，旨在提高一致性和候选蛋白质的准确性。通路分析证实，上调的蛋白质主要参与凝血。其中，我们选择了凝血酶原，纤溶酶原，纤维蛋白原α-链和富含组氨酸的糖蛋白作为候选生物标志物。在一组61个血清样本（31个健康对照和30个中风患者）的验证集中进行了多反应监测分析，以评估候选生物标志物的诊断价值。与健康对照组相比，中风患者的所有四种蛋白质均显示较高的表达水平。接收器工作特性曲线下的面积大于0.9，证实了它们的临床价值。这四种凝血蛋白可能有助于更准确，更快速地诊断中风。