Circulating microRNAs and isomiRs as biomarkers for the initial insult and epileptogenesis in four experimental epilepsy models: The EPITARGET study.

IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY
Epilepsia Pub Date : 2024-10-01 DOI:10.1111/epi.18134
Erwin A van Vliet, Mirte Scheper, James D Mills, Noora Puhakka, Kinga Szydlowska, Manuela Ferracin, Francesca Lovisari, Marie Soukupova, Silvia Zucchini, Prashant K Srivastava, Michael R Johnson, Katarzyna Lukasiuk, Jan A Gorter, Eleonora Aronica, Asla Pitkänen, Michele Simonato
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引用次数: 0

Abstract

Objective: Structural epilepsies can manifest months or years after the occurrence of an initial epileptogenic insult, making them amenable for secondary prevention. However, development of preventive treatments has been challenged by a lack of biomarkers for identifying the subset of individuals with the highest risk of epilepsy after the epileptogenic insult.

Methods: Four different rat models of epileptogenesis were investigated to identify differentially expressed circulating microRNA (miRNA) and isomiR profiles as biomarkers for epileptogenesis. Plasma samples were collected on day 2 and day 9 during the latency period from animals that did or did not develop epilepsy during long-term video-electroencephalographic monitoring. miRNAs and isomiRs were identified and measured in an unsupervised manner, using a genome-wide small RNA sequencing platform. Receiver operating characteristic analysis was performed to determine the performance of putative biomarkers.

Results: Two days after an epileptogenic insult, alterations in the levels of several plasma miRNAs and isomiRs predicted epileptogenesis in a model-specific manner. One miRNA, miR-3085, showed good sensitivity (but low specificity) as a prognostic biomarker for epileptogenesis in all four models (area under the curve = .729, sensitivity = 83%, specificity = 64%, p < .05).

Significance: Identified plasma miRNAs and isomiRs are mostly etiology-specific rather than common prognostic biomarkers of epileptogenesis. These data imply that in preclinical and clinical studies, it may be necessary to identify specific biomarkers for different epilepsy etiologies. Importantly, circulating miRNAs like miR-3085 with high negative predictive value for epileptogenesis in different etiologies could be useful candidates for initial screening purposes of epileptogenesis risk.

循环微RNA和isomiRs作为四种实验性癫痫模型初始损伤和癫痫发生的生物标记物:EPITARGET 研究。
目的:结构性癫痫可在最初的致痫损伤发生后数月或数年才出现,因此适合进行二级预防。然而,由于缺乏生物标志物来识别致痫损伤后患痫风险最高的人群,预防性治疗的开发一直面临挑战:方法:研究了四种不同的癫痫发生大鼠模型,以确定作为癫痫发生生物标志物的不同表达的循环微RNA(miRNA)和isomiR图谱。利用全基因组小RNA测序平台,以无监督方式鉴定和测量了miRNA和isomiRs。对推测的生物标志物的性能进行了接收者操作特征分析:结果:致痫损伤两天后,血浆中几种miRNA和isomiRs水平的改变以模型特异性的方式预测了癫痫的发生。一种 miRNA,即 miR-3085,作为癫痫发生的预后生物标志物,在所有四种模型中都显示出良好的灵敏度(但特异性较低)(曲线下面积 = .729,灵敏度 = 83%,特异性 = 64%,p 意义重大:鉴定出的血浆 miRNA 和 isomiRs 大多是癫痫发生的病因特异性生物标志物,而不是常见的预后生物标志物。这些数据表明,在临床前和临床研究中,可能有必要针对不同的癫痫病因确定特定的生物标志物。重要的是,循环 miRNA(如 miR-3085)对不同病因的癫痫发生具有较高的阴性预测值,可作为癫痫发生风险初步筛查的有用候选指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Epilepsia
Epilepsia 医学-临床神经学
CiteScore
10.90
自引率
10.70%
发文量
319
审稿时长
2-4 weeks
期刊介绍: Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.
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