AUTHOR=Malicek David , Wittig Ilka , Luger Sebastian , Foerch Christian 

TITLE=Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.713124

DOI=10.3389/fneur.2021.713124

ISSN=1664-2295

ABSTRACT=Background 
A reliable distinction between ischemic stroke (IS) and intracerebral hemorrhage (ICH) is required for diagnosis-specific treatment and effective secondary prevention in stroke patients. 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 & Methods 
Plasma samples from IS and ICH patients were drawn during hospitalization and were analyzed by 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 3 IS and 4 ICH patients with a median NIHSS of 12 (IQR 10.5-18.5) as well as serum samples from 2 healthy volunteers were analyzed. Among 495 identified protein groups, a total of 368 protein groups exhibited enough data points to be entered into a quantitative analysis. Of the remaining 22 top-listed proteins, a significant difference between IS and ICH was found for Carboxypeptidase N subunit 2, Coagulationfactor XII, Plasminogen, Mannan-binding lectin serine protease 1, Serum amyloid P-component, Paraoxonase 1, Carbonicanhydrase 1, Fibulin-1 and Granulins.

Discussion 
In this exploratory proteomics-based pilot study, 9 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 stroke patients 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.