鉴定用于评估切除性癫痫手术后癫痫发作情况的血清生物标志物

doi:10.5246/jcps.2020.08.050

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (8): 528-541.DOI: 10.5246/jcps.2020.08.050

鉴定用于评估切除性癫痫手术后癫痫发作情况的血清生物标志物

陈倩^1#, 赵旭阳^1#, 宋宇靖¹, 李少一², 雷婉钰¹, 马维宁^2*, 黄卓^1*

1. 北京大学医学部药学院天然药物及仿生药物国家重点实验室; 分子与细胞药理学系; 北京大学医学部基础医学院病理学系系统生物医学研究所; 清华大学-北京大学生命科学联合中心; 北京大学肿瘤系统生物学北京市重点实验室, 北京 100191
2. 中国医科大学附属盛京医院神经外科, 辽宁沈阳 110000

收稿日期:2020-04-21 修回日期:2020-05-24 出版日期:2020-08-31 发布日期:2020-06-11
通讯作者: Tel.: +86-24-96615-36316; +86-10-82805925; Fax: +86-10-82805925; +86-24-23892617, E-mail: weining@nln-med.com; huangz@hsc.pku.edu.cn
基金资助:
Grant (973 Program, Grant No. 015CB559200 to Z.H.) from the Ministry of Science and Technology of China, grant (Grant No. 31871083 to Z.H.) from the National Natural Science Foundation of China and grant (Grant No. 7182087 to Z.H.) from the Beijing Natural Science Foundation.

Identification of serum biomarkers for evaluating seizure outcome after resective epilepsy surgery

Qian Chen^1#, Xuyang Zhao^1#, Yujing Song¹, Shaoyi Li², Wanyu Lei¹, Weining Ma^2*, Zhuo Huang^1*

1. State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences; Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences; Beijing Key Laboratory of Tumor Systems Biology; Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing 100191, China
2. Department of Neurology, Shengjing Hospital affiliated to China Medical University, Shenyang 110000, China

Received:2020-04-21 Revised:2020-05-24 Online:2020-08-31 Published:2020-06-11
Contact: Tel.: +86-24-96615-36316; +86-10-82805925; Fax: +86-10-82805925; +86-24-23892617, E-mail: weining@nln-med.com; huangz@hsc.pku.edu.cn
Supported by:
Grant (973 Program, Grant No. 015CB559200 to Z.H.) from the Ministry of Science and Technology of China, grant (Grant No. 31871083 to Z.H.) from the National Natural Science Foundation of China and grant (Grant No. 7182087 to Z.H.) from the Beijing Natural Science Foundation.

摘要/Abstract

摘要：

尽管耐药性颞叶癫痫(TLE)的患者通过切除手术联合抗癫痫药(AED)的治疗可以很好地控制癫痫发作,但由于缺乏客观的评估手术结果的方法,尚不清楚在手术后何时停止服用AED。我们的目标是确定客观有效的生物标志物以评估手术结果,以指导术后药物治疗。因此,我们检测了术后无癫痫发作的TLE患者的术前和术后血清中的蛋白,得到了469个表达变化的蛋白,并从中筛选了6个候选蛋白(HBA1, HBB, PRDX2, CA1, CAT和BLVRB)。这六种蛋白质在术后三个月内显著减少,表明这些蛋白质可能是评估TLE患者早期手术结局的潜在生物标志物。重要的是,我们发现HBA1与HBB比值作为生物标志物优于单个蛋白质,受试者工作曲线分析中敏感度为90.0％,特异性为90％,曲线下面积为0.960。我们还提出这些蛋白可能源自癫痫病灶,这是由于我们发现在癫痫大鼠模型的脑脊液中高表达HBA1、HBB、PRDX2、CA1和CAT。此外,与术后癫痫复发的TLE患者和患有其他类型癫痫的患者的术前血清相比, HBA1, HBB, PRDX2, CA1和BLVRB蛋白在术后癫痫复发的TLE患者的术前血清中高表达,表明手术结果或癫痫发作的原始部位可以在手术前通过监测血清中的这些蛋白质水平进行评估。我们的研究提供了实验数据,用于建立术后评估癫痫发作的客观指标,并为TLE的病源诊断和TLE手术结果的预测提出了潜在的标志物。

关键词: 颞叶癫痫, 手术疗效, 生物标志物, 血清

Abstract:

Although patients with drug-resistant temporal lobe epilepsy (TLE) achieve good seizure control with resective surgery combined with anti-epileptic drugs (AEDs) treatment, it is still not clear when to withdraw AEDs after the surgery due to a lack of objective strategy for assessing the surgery outcome. Our aim is to identify objective and efficient biomarkers for assessment of surgery outcome to guide postoperative pharmacotherapy. Here, we detected 469 proteins differentially expressed between pre- and post-operative sera of TLE patients with postoperative seizure freedom, and identified six candidate proteins (HBA1, HBB, PRDX2, CA1, CAT and BLVRB) for validation. These six proteins were significantly reduced within three months after surgery, indicating these proteins may be potential biomarkers to assess the surgery outcome for TLE patients in the early stage. Interestingly,we found HBA1 to HBB ratio was superior to individual proteins to evaluate the postoperative surgery outcome with 90.0% sensitivity, 90% specificity and area under the curve of 0.960. We also suppose these proteins were derived from epilepsy foci due to the rat experiment results that HBA1, HBB, PRDX2, CA1 and CAT were highly expressed in cerebrospinal fluid of epilepsy rat models. Additionally, HBA1, HBB, PRDX2, CA1 and BLVRB proteins were highly expressed in the sera of TLE patients with postoperative seizure freedom when compared to TLE patients with postoperative seizure and patients with other types of epilepsy, suggesting surgery outcome or the original sites of seizure might be assessed before the operation through monitoring these protein levels in the sera. Our study provides experimental data for establishing objective indicators for assessing seizure freedom after resective surgery and also proposed potential markers for specific diagnoses of TLE and prediction of TLE surgery outcome.

Key words: Temporal lobe epilepsy, Surgery outcome, Biomarker, Serum

中图分类号:

R969

Supporting:

陈倩, 赵旭阳, 宋宇靖, 李少一, 雷婉钰, 马维宁, 黄卓. 鉴定用于评估切除性癫痫手术后癫痫发作情况的血清生物标志物[J]. 中国药学(英文版), 2020, 29(8): 528-541.

Qian Chen, Xuyang Zhao, Yujing Song, Shaoyi Li, Wanyu Lei, Weining Ma, Zhuo Huang. Identification of serum biomarkers for evaluating seizure outcome after resective epilepsy surgery[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(8): 528-541.

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鉴定用于评估切除性癫痫手术后癫痫发作情况的血清生物标志物

Identification of serum biomarkers for evaluating seizure outcome after resective epilepsy surgery

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