Discovery and validation of blood microRNAs as molecular biomarkers of epilepsy: Ways to close current knowledge gaps.
Discovery and validation of blood microRNAs as molecular biomarkers of epilepsy: Ways to close current knowledge gaps.
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DOI：
10.1002/epi4.12275
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发表时间：
2018-12-01
期刊：
影响因子：
3
通讯作者：
Henshall, David C
中科院分区：
文献类型：
--
作者：
Enright, Noelle;Simonato, Michele;Henshall, David C
对癫痫生物标志物的需求尚未得到满足。血液等生物流体是分子生物标志物的潜在来源。MicroRNAs （miRNAs）满足了血液分子生物标志物在大脑中富集和癫痫脑组织中失调的几个关键要求，并且在临床前模型中，对miRNAs的操作可以具有癫痫抑制和疾病改善作用。生物流体mirna还具有有利于翻译的品质，包括稳定性和简单廉价的检测技术。在此，我们回顾了临床和动物模型的研究结果。研究的特点是混合了无偏见的分析和假设驱动的努力。与药物反应性癫痫发作相比，癫痫患者和耐药患者血液中几种脑富集mirna的水平发生了改变，在敏感性和特异性方面，受体工作特征（ROC）曲线分析都令人鼓舞。局灶性和广泛性癫痫都与血液miRNA谱的改变有关，并与包括癫痫发作负担在内的临床参数相关。然而，结果仍处于初步阶段。需要持续的发现和验证工作，包括多中心研究和对研究设计、样本收集方法和质量控制的关注。研究集中在癫痫发生，以及与协变量，如性别，病因学和采样时间的关系仍然有限。我们确定了10个知识差距，并提出了缩小这些差距的实验。如果得到充分的解决，生物流体mirna可能是未来诊断生物标志物的重要来源，也可以支持即将进行的抗癫痫发生或疾病修饰疗法的试验。
There is a major unmet need for biomarkers of epilepsy. Biofluids such as blood offer a potential source of molecular biomarkers. MicroRNAs (miRNAs) fulfill several key requirements for a blood-based molecular biomarker being enriched in the brain and dysregulated in epileptic brain tissue, and manipulation of miRNAs can have seizure-suppressive and disease-modifying effects in preclinical models. Biofluid miRNAs also possess qualities that are favorable for translation, including stability and easy and cheap assay techniques. Herein we review findings from both clinical and animal models. Studies have featured a mix of unbiased profiling and hypothesis-driven efforts. Blood levels of several brain-enriched miRNAs are altered in patients with epilepsy and in patients with drug-resistant compared to drug-responsive seizures, with encouraging receiver-operating characteristic (ROC) curve analyses, both in terms of sensitivity and specificity. Both focal and generalized epilepsies are associated with altered blood miRNA profiles, and associations with clinical parameters including seizure burden have been reported. Results remain preliminary, however. There is a need for continued discovery and validation efforts that include multicenter studies and attention to study design, sample collection methodology, and quality control. Studies focused on epileptogenesis as well as associations with covariables such as sex, etiology, and timing of sampling remain limited. We identify 10 knowledge gaps and propose experiments to close these. If adequately addressed, biofluid miRNAs may be an important future source of diagnostic biomarkers that could also support forthcoming trials of antiepileptogenesis or disease-modifying therapies.