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Biomarkers. 2018 Dec;23(8):793-803. doi: 10.1080/1354750X.2018.1499130. Epub 2018 Aug 23.

Validation of a proteomic biomarker panel to diagnose minor-stroke and transient ischaemic attack: phase 2 of SpecTRA, a large scale translational study.

Author information

1
a Department of Neurosciences , Stroke Rapid Assessment Clinic, Island Health Authority , Victoria , Canada.
2
b Department of Research and Capacity Building , Island Health Authority , Victoria , Canada.
3
c Departments of Clinical Neurosciences, Radiology, and Community Health Services , University of Calgary , Calgary , Canada.
4
d Department of Mathematics and Statistics , University of Victoria , Victoria , Canada.
5
e George & Fay Yee Centre for Healthcare Innovation , University of Manitoba , Winnipeg , Canada.
6
f Division of Medical Sciences , University of Victoria , Victoria , Canada.
7
g Genome British Columbia Proteomics Centre, University of Victoria , Victoria , Canada.
8
h Department of Medicine , University of Toronto , Toronto , Canada.
9
i Department of Radiology , Foothills Medical Centre , Calgary , Canada.
10
j Department of Clinical Neurosciences , University of Calgary , Calgary , Canada.
11
k Department of Laboratory Medicine, Pathology & Medical Genetics , Island Health Authority , Victoria , Canada.
12
l Department of Biochemistry and Microbiology , University of Victoria , Victoria , Canada.
13
m Gerald Bronfman Department of Oncology , McGill University , Montreal , Canada.
14
n Proteomics Centre, Segal Cancer Centre , Lady Davis Institute , Montreal , Canada.

Abstract

OBJECTIVE:

To validate our previously developed 16 plasma-protein biomarker panel to differentiate between transient ischaemic attack (TIA) and non-cerebrovascular emergency department (ED) patients.

METHOD:

Two consecutive cohorts of ED patients prospectively enrolled at two urban medical centers into the second phase of SpecTRA study (training, cohort 2A, nā€‰=ā€‰575; test, cohort 2B, nā€‰=ā€‰528). Plasma samples were analyzed using liquid chromatography/multiple reaction monitoring-mass spectrometry. Logistic regression models which fit cohort 2A were validated on cohort 2B.

RESULTS:

Three of the panel proteins failed quality control and were removed from the panel. During validation, panel models did not outperform a simple motor/speech (M/S) deficit variable. Post-hoc analyses suggested the measured behaviour of L-selectin and coagulation factor V contributed to poor model performance. Removal of these proteins increased the external performance of a model containing the panel and the M/S variable.

CONCLUSIONS:

Univariate analyses suggest insulin-like growth factor-binding protein 3 and serum paraoxonase/lactonase 3 are reliable and reproducible biomarkers for TIA status. Logistic regression models indicated L-selectin, apolipoprotein B-100, coagulation factor IX, and thrombospondin-1 to be significant multivariate predictors of TIA. We discuss multivariate feature subset analyses as an exploratory technique to better understand a panel's full predictive potential.

KEYWORDS:

TIA; TIA biomarkers; plasma biomarkers; stroke biomarkers; stroke proteomic; transient ischaemic attack

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