Journal
BIOMARKERS
Volume 23, Issue 8, Pages 793-803Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/1354750X.2018.1499130
Keywords
TIA; transient ischaemic attack; TIA biomarkers; stroke biomarkers; stroke proteomic; plasma biomarkers
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Funding
- Genome Alberta [4125-Penn]
- Genome Canada [4125-Penn]
- Genome British Columbia [4125-Penn, 204PRO, 214PRO]
- Leading Edge Endowment Fund (University of Victoria)
- Segal McGill Chair in Molecular Oncology at McGill University (Montreal, Quebec, Canada)
- Warren Y. Soper Charitable Trust
- Alvin Segal Family Foundation
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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, n = 575; test, cohort 2B, n = 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.
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