학술논문

Identification of novel blood biomarker panels to detect ischemic stroke in patients and their responsiveness to therapeutic intervention
Document Type
article
Source
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Brain Disorders
Stroke
Clinical Research
4.1 Discovery and preclinical testing of markers and technologies
Detection
screening and diagnosis
Aged
Biomarkers
Biomarkers
Pharmacological
Blood Proteins
Brain Ischemia
Cytokine Receptor gp130
Female
Humans
Male
Matrix Metalloproteinase 2
Middle Aged
Osteopontin
ROC Curve
Risk Factors
TNF Receptor-Associated Factor 1
TNF Receptor-Associated Factor 2
Tissue Plasminogen Activator
Blood biomarker panels
Ischemic stroke
Inflammation
Luminex
Plasma
Neurosciences
Psychology
Cognitive Sciences
Neurology & Neurosurgery
Biological psychology
Language
Abstract
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.