Abstract
Background: A reliable distinction between ischemic stroke (IS) and intracerebral hemorrhage (ICH) is required for diagnosis-specific treatment and effective secondary prevention in patients with stroke. However, in resource-limited settings brain imaging, which is the current diagnostic gold standard for this purpose, is not always available in time. Hence, an easily accessible and broadly applicable blood biomarker-based diagnostic test differing stroke subtypes would be desirable. Using an explorative proteomics approach, this pilot study aimed to identify novel blood biomarker candidates for distinguishing IS from ICH.Material and Methods: Plasma samples from patients with IS and ICH were drawn during hospitalization and were analyzed by using liquid chromatography/mass spectrometry. Proteins were identified using the human reference proteome database UniProtKB, and label-free quantification (LFQ) data were further analyzed using bioinformatic tools.Results: Plasma specimens of three patients with IS and four patients with ICH with a median National Institute of Health Stroke Scale (NIHSS) of 12 [interquartile range (IQR) 10.5–18.5] as well as serum samples from two healthy volunteers were analyzed. Among 495 identified protein groups, a total of 368 protein groups exhibited enough data points to be entered into quantitative analysis. Of the remaining 22 top-listed proteins, a significant difference between IS and ICH was found for Carboxypeptidase N subunit 2 (CPN2), Coagulation factor XII (FXII), Plasminogen, Mannan-binding lectin serine protease 1, Serum amyloid P-component, Paraoxonase 1, Carbonic anhydrase 1, Fibulin-1, and Granulins.Discussion: In this exploratory proteomics-based pilot study, nine candidate biomarkers for differentiation of IS and ICH were identified. The proteins belong to the immune system, the coagulation cascade, and the apoptosis system, respectively. Further investigations in larger cohorts of patients with stroke using additional biochemical analysis methods, such as ELISA or Western Blotting are now necessary to validate these markers, and to characterize diagnostic accuracy with regard to the development of a point-of-care-system for use in resource-limited areas.
Highlights
In recent years, treatment options for patients with ischemic stroke (IS) have largely expanded
Plasma serum amyloid P-component (APCS) is higher in intracerebral hemorrhage (ICH) than in healthy controls
Increased APCS serum levels in the elderly are associated with angina pectoris and myocardial infarction but not with stroke APCS is a component of fibrin-clots
Summary
Treatment options for patients with ischemic stroke (IS) have largely expanded. Mobile stroke units have been released to apply thrombolysis already in the preclinical setting with the shortest possible delays after symptom onset [10, 11]. In contrast to these “high-tech” advances to stand by in many high-income countries, low- to middle-income countries still face immense shortcomings in medical resources. The stratification into IS and intracerebral hemorrhage (ICH) is not possible at all or only after long transports and transfer delays [14] This prevents acute target-orientated stroke treatment, and from the timely initiation of diagnosis-specific secondary prevention (i.e., platelet inhibitors in patients with IS). Using an explorative proteomics approach, this pilot study aimed to identify novel blood biomarker candidates for distinguishing IS from ICH
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