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.

中文翻译：

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用于心脏骤停后神经系统预后的新型预测血清蛋白的血清蛋白质组学分析

在评估患者的生存时间和制定适当的治疗策略以避免患者停止维持生命治疗 (WLST) 时，早期预测心脏骤停 (CA) 后昏迷患者的神经系统结果对于临床医生至关重要。然而，仍然缺乏用于早期和准确识别这些患者的敏感和特异的血清生物标志物。使用等压标签进行基于相对和绝对定量 (iTRAQ) 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 种上调的分泌血清蛋白和 16 种下调的分泌血清蛋白在三名神经功能良好与不良的昏迷 CA 幸存者之间恢复。然后，选择了 4 种蛋白质，并通过酶联免疫吸附试验 (ELISA) 方法在包含 32 名神经系统预后良好的患者和 46 名神经系统预后不良的患者的大规模样本中进行验证，并证实血清血管紧张素原 (AGT) 和 α- 1-抗胰蛋白酶 (SERPINA1) 与 CA 幸存者的神经功能和预后相关。使用基于 AGT、SERPINA1 和神经元特异性烯醇化酶 (NSE) 组合的线性和逻辑回归模型开发和计算预后风险评分，曲线下面积为 0.865 ( 并证实血清血管紧张素原 (AGT) 和 α-1-抗胰蛋白酶 (SERPINA1) 与 CA 幸存者的神经功能和预后相关。使用基于 AGT、SERPINA1 和神经元特异性烯醇化酶 (NSE) 组合的线性和逻辑回归模型开发和计算预后风险评分，曲线下面积为 0.865 ( 并证实血清血管紧张素原 (AGT) 和 α-1-抗胰蛋白酶 (SERPINA1) 与 CA 幸存者的神经功能和预后相关。使用基于 AGT、SERPINA1 和神经元特异性烯醇化酶 (NSE) 组合的线性和逻辑回归模型开发和计算预后风险评分，曲线下面积为 0.865 (P  < .001），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的结果不仅揭示了神经系统恢复期间生物标志物的变化，而且有助于增强目前对昏迷 CA 幸存者的治疗策略。