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Testing a Multivariate Proteomic Panel for Traumatic Brain Injury Biomarker Discovery: A TRACK-TBI Pilot Study

机译:试验对创伤性脑损伤生物标志物发现的多变量蛋白质组学小组:赛道 - TBI试验研究

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The complex and heterogeneous nature of traumatic brain injury (TBI) has rendered the identification of diagnostic and prognostic biomarkers elusive. A single acute biomarker may not be sufficient to categorize injury severity and/or predict outcome. Using multivariate dimension reduction analyses, we tested the sensitivity and specificity of a multi-analyte panel of proteins as an ensemble biomarker for TBI. Serum was collected within 24 h of injury in a cohort of 130 patients enrolled in the multi-center prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study and run on an array that measured 72 proteins. Using unsupervised principal components analysis, we first identified the subset of protein changes accounting for the most variance across patients. This yielded a group of 21 proteins that reflected an inverse relationship between inflammatory cytokines and regulators of anti-inflammation, and generated an individual inflammatory profile score for each patient. We then tested the association between these scores and computed tomography (CT) findings at hospital admission, as well as their prognostic association with functional recovery at 3 and 6 months (Glasgow Outcome Scale-Extended), and cognitive recovery at 6 months (California Verbal Learning Test, Second Edition) after injury. Inflammatory signatures were significantly increased in patients with positive CT findings, as well as in those who showed poor or incomplete recovery. Inflammation biomarker scores also showed significant sensitivity and specificity as a discriminator of these outcome measures (all areas under the curve [AUCs] >0.62). This proof of concept for the feasibility of multivariate biomarker identification demonstrates the prognostic validity of using a proteomic panel as a potential biomarker for TBI.
机译:创伤性脑损伤(TBI)的复杂和异质性质使鉴定诊断和预后生物标志物难以捉摸。单个急性生物标志物可能不足以对损伤严重程度和/或预测结果进行分类。使用多元尺寸减少分析,我们测试了蛋白质的多元分析物面板的敏感性和特异性作为TBI的集合生物标志物。在130名患者的伤害中收集血清,注册了创伤性脑损伤飞行员(Track-TBI试点)研究的多中心前瞻性转化研究和临床知识,并在测量72蛋白的阵列上运行。使用无监督的主要成分分析,我们首先确定了蛋白质变化的子集核算患者中最方差。这产生了一组21种蛋白质,其反映了炎症细胞因子和抗炎调节剂之间的反比关系,并为每位患者产生了个体炎症性剖面。然后,我们在医院入院的这些评分和计算断层扫描(CT)调节之间的关联以及它们在3和6个月(Glasgow结果规模延长)和6个月内的认知恢复(加利福尼亚州言语)的预​​后关联学习测试,第二版)受伤后。阳性CT调节患者的炎症签名显着增加,以及那些表现出差或不完全恢复的人。炎症生物标志物评分还表现出显着的敏感性和特异性,作为这些结果测量的鉴别者(曲线曲线下的所有区域> 0.62)。这种对多元生物标志物识别可行性的概念证明证明了使用蛋白质组织作为TBI潜在生物标志物的预后有效性。

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