Abstract
Objectives
Severe traumatic brain injury (sTBI) patients suffer high mortality. Accurate prognostic biomarkers have not been identified. In this exploratory study, we performed targeted proteomics on plasma obtained from sTBI patients to identify potential outcome biomarkers.
Methods
Blood sample was collected from patients admitted to the ICU suffering a sTBI, using standardized clinical and computerized tomography (CT) imaging criteria. Age- and sex-matched healthy control subjects and sTBI patients were enrolled. Targeted proteomics was performed on plasma with proximity extension assays (1,161 proteins).
Results
Cohorts were well-balanced for age and sex. The majority of sTBI patients were injured in motor vehicle collisions and the most frequent head CT finding was subarachnoid hemorrhage. Mortality rate for sTBI patients was 40%. Feature selection identified the top performing 15 proteins for identifying sTBI patients from healthy control subjects with a classification accuracy of 100%. The sTBI proteome was dominated by markers of vascular pathology, immunity/inflammation, cell survival and macrophage/microglia activation. Receiver operating characteristic (ROC) curve analyses demonstrated areas-under-the-curves (AUC) for identifying sTBI that ranged from 0.870-1.000 (p≤0.005). When mortality was used as outcome, ROC curve analyses identified the top 3 proteins as Willebrand factor (vWF), Wnt inhibitory factor-1 (WIF-1), and colony stimulating factor-1 (CSF-1). Combining vWF with either WIF-1 or CSF-1 resulted in excellent mortality prediction with AUC of 1.000 for both combinations (p=0.011).
Conclusions
Targeted proteomics with feature classification and selection distinguished sTBI patients from matched healthy control subjects. Two protein combinations were identified that accurately predicted sTBI patient mortality. Our exploratory findings require confirmation in larger sTBI patient populations.
Funding source: Children’s Health Foundation
Acknowledgments
We thank Dr. Carolina Gillio-Meina for biological sample collection and processing (Translational Research Centre, London, Ontario, Canada; https://translationalresearchcentre.com) and the frontline Critical Care Nursing Staff at London Health Sciences Centre (London, Ontario, Canada).
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Research funding: This research is funded by Children’s Health Foundation.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The study was approved by the Western University, Human Research Ethics Board (HREB; REB# 6970; REB# 100036).
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2021-0103).
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