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循环中的miR-146a-5p和miR-132-3p作为癫痫潜在的诊断生物标志物。

Circulating miR-146a-5p and miR-132-3p as potential diagnostic biomarkers in epilepsy.

作者信息

Nomair Azhar Mohamed, Mekky Jaidaa Farouk, El-Hamshary Shaymaa Ali, Nomeir Hanan Mohamed

机构信息

Department of Chemical Pathology, Medical Research Institute, Alexandria University, Egypt.

Department of Neuropsychiatry, Faculty of Medicine, Alexandria University, Egypt.

出版信息

Epilepsy Res. 2023 Mar;191:107089. doi: 10.1016/j.eplepsyres.2023.107089. Epub 2023 Feb 9.

Abstract

OBJECTIVE

MiRNAs are important gene-regulating agents in epilepsy development, according to new research. The purpose of this study is to investigate the relationship between serum expression of miR-146a-5p and miR-132-3p and epilepsy in Egyptian patients as potential diagnostic and therapeutic biomarkers.

METHODS

MiR-146a-5p and miR-132-3p were measured in the serum of 40 adult epilepsy patients and 40 controls using real-time polymerase chain reaction. The comparative cycle threshold (CT) approach (2) was used to compute relative expression levels, which were normalized to cel-miR-39 expression and compared to healthy controls. The diagnostic performance of miR-146a-5p and miR-132-3p was assessed using receiver operating characteristic curve analysis.

RESULTS

The relative expression levels of miR-146a-5p and miR-132-3p in serum were considerably greater in epilepsy patients than in the control group. There was a significant difference in the miRNA-146a-5p relative expression in the focal group when the non-responders were compared with the responders' groups, and a significant difference when comparing the non-responders' focal and the non-responders' generalized groups, however, univariate logistic regression analysis revealed that increased seizure frequency is the only risk factor among all factors affecting the drug response There was a significant difference in epilepsy duration between miR-132-3p high and low expression. With an area under the curve of 0.714 (95% C. I 0.598-0.830; P = 0.001), the combined miR-146a-5p and miR-132-3p serum levels performed better than each separately as a diagnostic biomarker to distinguish epilepsy patients from controls.

SIGNIFICANCE

The findings imply that both miR-146a-5p and miR-132-3p may be involved in epileptogenesis regardless of epilepsy subtypes. Although the combined circulating miRNAs may be useful as a diagnostic biomarker, they are not a predictor of drug response. MiR-132-3p might be used to predict epilepsy's prognosis by demonstrating its chronicity.

摘要

目的

根据最新研究,微小RNA(miRNAs)是癫痫发展过程中重要的基因调控因子。本研究旨在探讨埃及患者血清中miR-146a-5p和miR-132-3p的表达与癫痫之间的关系,将其作为潜在的诊断和治疗生物标志物。

方法

采用实时聚合酶链反应检测40例成年癫痫患者和40例对照者血清中的miR-146a-5p和miR-132-3p。使用比较循环阈值(CT)法计算相对表达水平,以cel-miR-39表达为参照进行标准化,并与健康对照者进行比较。采用受试者工作特征曲线分析评估miR-146a-5p和miR-132-3p的诊断性能。

结果

癫痫患者血清中miR-146a-5p和miR-132-3p的相对表达水平显著高于对照组。将无反应者与有反应者组比较时,局灶性组中miRNA-146a-5p相对表达存在显著差异,比较无反应者的局灶性组和全身性组时也存在显著差异,然而,单因素逻辑回归分析显示,发作频率增加是所有影响药物反应的因素中唯一的危险因素。miR-132-3p高表达和低表达组之间癫痫病程存在显著差异。miR-146a-5p和miR-132-3p血清水平联合检测作为诊断生物标志物区分癫痫患者和对照者的性能优于单独检测,曲线下面积为0.714(95%可信区间0.598 - 0.830;P = 0.001)。

意义

研究结果表明,无论癫痫亚型如何,miR-146a-5p和miR-132-3p都可能参与癫痫的发生。虽然联合循环微小RNA可能作为诊断生物标志物有用,但它们不是药物反应的预测指标。miR-132-3p可能通过显示其慢性程度来预测癫痫的预后。

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