Ioriatti Enrico Salomao, Cirino Mucio Luiz Assis, Lizarte Neto Fermino Sanches, Velasco Tonicarlo Rodrigues, Sakamoto Americo Ceiki, Freitas-Lima Priscila, Tirapelli Daniela Pretti Cunha, Carlotti Carlos Gilberto
Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
Epilepsy Res. 2020 Oct;166:106373. doi: 10.1016/j.eplepsyres.2020.106373. Epub 2020 May 22.
MicroRNAs have been progressively investigated as post-transcriptional regulators playing important roles in epilepsy pathophysiology. Here we investigate three promising microRNAs (miR-27a-3p, miR-328-3p and miR-654-3p) previously described in the literature as possible peripheral biomarkers for epilepsy diagnose and surgical prognosis. Serum samples from 28 patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) were analyzed, 14 with good surgical prognosis (Engel I) and 14 with unfavorable surgical prognosis (Engel III-IV). Serum samples from 11 healthy volunteers were the control group. The microRNAs expression analysis was performed using real-time PCR. The present results did not endorse the role of miR-27a-3p as a peripheral biomarker for epilepsy diagnosis or surgical prognosis. MiR-328-3p, however, presented significant area under the curve (AUC) values when comparing controls to Engel I (90.3%), controls to Engel III-IV (96.8%) and controls to Engel I + Engel III-IV (i.e., epilepsy patients, AUC = 93.5%). Additionally, miR-654-3p displayed AUC = 74.7% when comparing controls to Engel I patients (p = 0.004), and AUC = 73.6% (p = 0.04) in the attempt to discriminate unfavorable from favorable surgical prognosis. In conclusion, the ANOVA and ROC analyzes with the respective AUC, specificity and sensitivity values allows us to conclude that miR-328-3p is the most important peripheral biomarker for the diagnosis of MTLE-HS. In terms of predicting the surgical prognosis of MTLE-HS patients, miR-654-3p proved to be the only microRNA evaluated to present statistical power to differentiate, as a peripheral biomarker, Engel I from Engel III-IV patients.
微小RNA作为转录后调节因子，在癫痫病理生理学中发挥着重要作用，对此研究日益深入。在此，我们对文献中先前描述的三种有前景的微小RNA（miR-27a-3p、miR-328-3p和miR-654-3p）进行研究，它们可能作为癫痫诊断和手术预后的外周生物标志物。分析了28例患有海马硬化的内侧颞叶癫痫（MTLE-HS）患者的血清样本，其中14例手术预后良好（Engel I级），14例手术预后不良（Engel III-IV级）。11名健康志愿者的血清样本作为对照组。使用实时PCR进行微小RNA表达分析。目前的结果不支持miR-27a-3p作为癫痫诊断或手术预后外周生物标志物的作用。然而，当比较对照组与Engel I级患者（曲线下面积[AUC]为90.3%）、对照组与Engel III-IV级患者（AUC为96.8%）以及对照组与Engel I+Engel III-IV级患者（即癫痫患者，AUC=93.5%）时，miR-328-3p显示出显著的AUC值。此外，在比较对照组与Engel I级患者时，miR-654-3p的AUC为74.7%（p=0.004），在试图区分手术预后不良与良好时，AUC为73.6%（p=0.04）。总之，方差分析和ROC分析以及各自的AUC、特异性和敏感性值使我们能够得出结论，miR-328-3p是诊断MTLE-HS最重要的外周生物标志物。就预测MTLE-HS患者的手术预后而言，miR-654-3p被证明是唯一经评估具有统计学能力作为外周生物标志物区分Engel I级和Engel III-IV级患者的微小RNA。
