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Serum proteomic analysis of novel predictive serum proteins for neurological prognosis following cardiac arrest

机译:心脏骤停后神经学预测的新型预测性血清蛋白的血清蛋白质组学分析

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Early prognostication of neurological outcome in comatose patients after cardiac arrest (CA) is vital for clinicians when assessing the survival time of sufferers and formulating appropriate treatment strategies to avoid the withdrawal of life‐sustaining treatment (WLST) from patients. However, there is still a lack of sensitive and specific serum biomarkers for early and accurate identification of these patients. Using an isobaric tag for relative and absolute quantitation (iTRAQ)‐based proteomic approach, we discovered 55 differentially expressed proteins, with 39 up‐regulated secreted serum proteins and 16 down‐regulated secreted serum proteins between three comatose CA survivors with good versus poor neurological recovery. Then, four proteins were selected and were validated via an enzyme‐linked immunosorbent assay (ELISA) approach in a larger‐scale sample containing 32 good neurological outcome patients and 46 poor neurological outcome patients, and it was confirmed that serum angiotensinogen (AGT) and alpha‐1‐antitrypsin (SERPINA1) were associated with neurological function and prognosis in CA survivors. A prognostic risk score was developed and calculated using a linear and logistic regression model based on a combination of AGT, SERPINA1 and neuron‐specific enolase (NSE) with an area under the curve of 0.865 ( P ?.001), and the prognostic risk score was positively correlated with the CPC value (R?=?0.708, P ?.001). We propose that the results of the risk score assessment not only reveal changes in biomarkers during neurological recovery but also assist in enhancing current therapeutic strategies for comatose CA survivors.
机译:在评估患者生存时间并制定适当的治疗策略时,心脏骤停(CA)在临床医生中对临床医生至关重要的预后对临床医生至关重要,以避免患者避免患者的寿命持续治疗(WLST)撤离。然而,仍然缺乏敏感和特异性的血清生物标志物,用于早期和准确地鉴定这些患者。使用同学标签进行相对和绝对定量(ITRAQ)基础的蛋白质组学方法,我们发现了55种差异表达的蛋白质,其中39例上调分泌的血清蛋白和16个下调的分泌的分泌血清蛋白在三个昏迷的CA幸存者之间,具有良好的与神经学相比恢复。然后,选择四种蛋白质并通过酶联免疫吸附试验(ELISA)方法在含有32例良好的神经治疗患者和46名神经系统结果患者的较大级样品中验证,并确认血清血管紧张素(AGT)和Alpha-1-Antikrypsin(Serpina1)与Ca幸存者的神经功能和预后有关。使用基于AgT,Serpina1和神经元特异性烯醇酶(NSE)的组合的线性和逻辑回归模型进行了预后的风险评分,并使用0.865(P <。001)的曲线下的面积。预后风险评分与CPC值呈正相关(R?= 0.708,P& 001)。我们建议风险评分评估结果不仅揭示了神经恢复期间生物标志物的变化,而且还有助于提高COMATOSE CA幸存者的当前治疗策略。

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