Acute Biomarkers of Traumatic Brain Injury: Relationship between Plasma Levels of Ubiquitin C-Terminal Hydrolase-L1 and Glial Fibrillary Acidic Protein
Acute Biomarkers of Traumatic Brain Injury: Relationship between Plasma Levels of Ubiquitin C-Terminal Hydrolase-L1 and Glial Fibrillary Acidic Protein
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DOI：
10.1089/neu.2013.3040
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发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Vassar, Mary J.
中科院分区：
文献类型：
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作者：
Diaz-Arrastia, Ramon;Wang, Kevin K. W.;Vassar, Mary J.
生物标志物对于准确诊断复杂疾病如创伤性脑损伤（TBI）非常重要。对于复杂和多方面的疾病，如TBI，单一的生物标志物可能无法反映脑组织对损伤的全谱反应。泛素C末端水解酶L1（UCH-L1）和胶质纤维酸性蛋白（GFAP）是研究最广泛的TBI生物标志物之一。由于UCH-L1和GFAP测量不同的分子事件，我们假设，分析这两种生物标志物将优于上级分析各自单独用于TBI的诊断和预后。在一项多中心观察性研究（TRACK-TBI）中，对206例TBI患者的血清UCH-L1和GFAP水平进行了测量。两种生物标志物的水平彼此弱相关（r=0.364）。分离的每种生物标志物具有良好的灵敏度，并且对于区分TBI患者和健康对照具有良好的灵敏度（UCH-L1和GFAP的曲线下面积[AUC]分别为0.87和0.91）。当生物标志物组合时，获得了诊断TBI的上级灵敏度和特异性（AUC 0.94）。两种生物标志物可区分CT扫描显示有颅内病变的TBI患者和无此类病变的TBI患者，但GFAP测量显著更敏感和特异性（UCH-L1的AUC 0.88 vs. 0.71）。对于与损伤后3个月结果的相关性，两种生物标志物都没有足够的敏感性和特异性（GFAP的AUC为0.65-0.74，UCH-L1为0.59-0.80，取决于所使用的格拉斯哥结果量表扩展[GOS-E]阈值）。我们的结果支持多个生物标志物测量在TBI研究中的作用。（ClinicalTrials.gov标识符NCT 01565551）
Biomarkers are important for accurate diagnosis of complex disorders such as traumatic brain injury (TBI). For a complex and multifaceted condition such as TBI, it is likely that a single biomarker will not reflect the full spectrum of the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are among of the most widely studied biomarkers for TBI. Because UCH-L1 and GFAP measure distinct molecular events, we hypothesized that analysis of both biomarkers would be superior to analysis of each alone for the diagnosis and prognosis of TBI. Serum levels of UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a multicenter observational study (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI]). Levels of the two biomarkers were weakly correlated to each other (r=0.364). Each biomarker in isolation had good sensitivity and sensitivity for discriminating between TBI patients and healthy controls (area under the curve [AUC] 0.87 and 0.91 for UCH-L1 and GFAP, respectively). When biomarkers were combined, superior sensitivity and specificity for diagnosing TBI was obtained (AUC 0.94). Both biomarkers discriminated between TBI patients with intracranial lesions on CT scan and those without such lesions, but GFAP measures were significantly more sensitive and specific (AUC 0.88 vs. 0.71 for UCH-L1). For association with outcome 3 months after injury, neither biomarker had adequate sensitivity and specificity (AUC 0.65-0.74, for GFAP, and 0.59-0.80 for UCH-L1, depending upon Glasgow Outcome Scale Extended [GOS-E] threshold used). Our results support a role for multiple biomarker measurements in TBI research. (ClinicalTrials.gov Identifier NCT01565551)