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鉴定用于预测心脏骤停后神经预后的新型生物标志物。

Identification of novel biomarkers for prediction of neurological prognosis following cardiac arrest.

作者信息

Eun Jung Woo, Yang Hee Doo, Kim Soo Hyun, Hong Sungyoup, Park Kyu Nam, Nam Suk Woo, Jeong Sikyoung

机构信息

Department of Pathology, Functional RNomics Research Center, Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

出版信息

Oncotarget. 2017 Mar 7;8(10):16144-16157. doi: 10.18632/oncotarget.14877.

Abstract

BACKGROUND

Early prognostication of neurological outcome in comatose patients after cardiac arrest (CA) is important for devising patient treatment strategies. However, there is still a lack of sensitive and specific biomarkers for easy identification of these patients. We evaluated whether molecular signatures from blood of CA patients might help to improve the prediction of neurological outcome.

METHODS

We examined 22 comatose patients resuscitated after CA and obtained peripheral blood samples 48 hours after CA. To identify novel blood biomarkers, we aimed to measure neurological outcomes according to the Cerebral Performance Category (CPC) score at 6 months after CA and to determine blood transcriptome-based molecular signature of poor neurological outcome group.

RESULTS

According to the CPC score, 10 patients exhibited a CPC score of one and 12 patients, a CPC score four to five. Blood transcriptomics revealed differently expressed profiles between the good outcome group and poor outcome group. A total of 150 genes were down-regulated and 237 genes were up-regulated in the poor neurological outcome group compared with good outcome group. From the blood transcriptome-based signatures, we identified that MAPK3, BCL2 and AKT1 were more specific and sensitive diagnostic biomarkers in poor neurological outcome with an area under the curve of 0.867 (p<0.0001), 0.800 (p=0.003), and 0.767 (p=0.016) respectively.

CONCLUSIONS

We identify three biomarkers as potential predictors of neurological outcome following CA. Further assessment of the prognostic value of transcriptomic analysis in larger cohorts of CA patients is needed.

摘要

背景

心脏骤停(CA)后昏迷患者神经功能预后的早期预测对于制定患者治疗策略至关重要。然而,仍缺乏用于轻松识别这些患者的敏感且特异的生物标志物。我们评估了CA患者血液中的分子特征是否有助于改善神经功能预后的预测。

方法

我们检查了22例CA后复苏的昏迷患者,并在CA后48小时获取外周血样本。为了识别新的血液生物标志物,我们旨在根据CA后6个月的脑功能分类(CPC)评分来衡量神经功能预后,并确定神经功能预后不良组基于血液转录组的分子特征。

结果

根据CPC评分,10例患者的CPC评分为1分,12例患者的CPC评分为4至5分。血液转录组学显示良好预后组和不良预后组之间存在不同的表达谱。与良好预后组相比,神经功能预后不良组共有150个基因下调,237个基因上调。从基于血液转录组的特征中,我们确定丝裂原活化蛋白激酶3(MAPK3)、B细胞淋巴瘤2(BCL2)和蛋白激酶B1(AKT1)是神经功能预后不良中更特异和敏感的诊断生物标志物,曲线下面积分别为0.867(p<0.0001)、0.800(p=0.003)和0.767(p=0.016)。

结论

我们确定了三种生物标志物作为CA后神经功能预后的潜在预测指标。需要在更大规模的CA患者队列中进一步评估转录组分析的预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f14/5369953/45310373019c/oncotarget-08-16144-g001.jpg

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