Proteomics-based approach to identify novel blood biomarker candidates for differentiating intracerebral hemorrhage from ischemic stroke — a pilot study

  • 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.

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Author:David Peter Maria MalicekGND, Ilka WittigORCiD, Sebastian LugerORCiDGND, Christian FörchORCiDGND
URN:urn:nbn:de:hebis:30:3-620721
DOI:https://doi.org/10.3389/fneur.2021.713124
ISSN:1664-2295
Parent Title (English):Frontiers in neurology
Publisher:Frontiers Research Foundation
Place of publication:Lausanne
Document Type:Article
Language:English
Date of Publication (online):2021/12/17
Date of first Publication:2021/12/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/10/01
Tag:biomarker; blood; differentiation; intracerebral hemorrhage; ischemic stroke; mass spectrometry
Volume:12
Issue:art. 713124
Article Number:713124
Page Number:14
First Page:1
Last Page:14
Note:
Gefördert durch den Open-Access-Publikationsfonds der Goethe-Universität
Note:
Funding: Deutsche Forschungsgesellschaft (DFG) ; SFB815/Z1 (IW)
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Medizin
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International