TY  - JOUR
PY  - 2021//
TI  - Novel severe traumatic brain injury blood outcome biomarkers identified with proximity extension assay
JO  - Clinical chemistry and laboratory medicine
A1  - Fraser, Douglas D.
A1  - Chen, Michelle
A1  - Ren, Annie
A1  - Miller, Michael R.
A1  - Martin, Claudio
A1  - Daley, Mark
A1  - Diamandis, Eleftherios P.
A1  - Prassas, Ioannis
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - 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. <br><br>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). <br><br>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 vWF, WIF-1, and 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). <br><br>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.<p />  <p>Language: en</p>
LA  - en
SN  - 1434-6621
UR  - http://dx.doi.org/10.1515/cclm-2021-0103
ID  - ref1
ER  -