Differential Proteomics for Distinguishing Ischemic Stroke from Controls: a Pilot Study of the SpecTRA Project
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ORIGINAL ARTICLE
Differential Proteomics for Distinguishing Ischemic Stroke from Controls: a Pilot Study of the SpecTRA Project A. M. Penn 1 & V. Saly 1 & A. Trivedi 1 & M. L. Lesperance 2 & K. Votova 3,4 & A. M. Jackson 5 & N.S. Croteau 2,3 & R. F. Balshaw 6,7 & M. B. Bibok 3 & D. S. Smith 5 & K. K. Lam 6 & J. Morrison 3 & L. Lu 2,3 & S. B. Coutts 8 & C. H. Borchers 5,9 Received: 14 November 2017 / Accepted: 5 January 2018 # The Author(s) 2018. This article is an open access publication
Abstract A diagnostic blood test for stroke is desirable but will likely require multiple proteins rather than a single Btroponin.^ Validating large protein panels requires large patient numbers. Mass spectrometry (MS) is a cost-effective tool for this task. We compared differences in the abundance of 147 protein markers to distinguish 20 acute cerebrovascular syndrome (ACVS) patients who presented to the Emergency Department of one urban hospital within < 24 h from onset) and from 20 control patients who were enrolled via an outpatient neurology clinic. We targeted proteins from the stroke literature plus cardiovascular markers previously studied in our lab. One hundred forty-one proteins were quantified using MS, 8 were quantified using antibody protein enrichment with MS, and 32 were measured using ELISA, with some proteins measured by multiple techniques. Thirty proteins (4 by ELISA and 26 by the MS techniques) were differentially abundant between mimic and stroke after adjusting for age in robust regression analyses (FDR < 0.20). A logistic regression model using the first two principal components of the proteins significantly improved discrimination between strokes and controls compared to a model based on age alone (p < 0.001, cross-validated AUC 0.93 vs. 0.78). Significant proteins included markers of inflammation (47%), coagulation (40%), atrial fibrillation (7%), neurovascular unit injury (3%), and other (3%). These results suggest the potential value of plasma proteins as biomarkers for ACVS diagnosis and the role of plasma-based MS in this area. Keywords Proteomics . Plasma proteins . Mass spectrometry . Stroke . Hematologic tests . Infarction
Introduction In the management of acute cerebrovascular syndrome (ACVS) [1], the high prevalence of conditions that mimic
* K. Votova [email protected] 1
2
Department of Neuroscience, Stroke Rapid Assessment Unit (SRAU), Island Health, 1 Hospital Way, Victoria, BC V8Z 6R5, Canada Department of Mathematics and Statistics, University of Victoria, 3800 Finnerty Rd., Victoria, BC V8P 5C2, Canada
3
Department of Research and Capacity Building, Island Health, 1952 Bay Street, Victoria, BC V8R 1J8, Canada
4
Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada
stroke presents a challenge, particularly for first-line physicians. Such mimics include migraine, Todd’s paresis following seizure, delirium, compressive neuropathies, and many other entities [2]. Unlike cardiology where an ECG and single
5
University of Victoria-Genome British Colum
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