Avansini Simoni H, de Sousa Lima Beatriz Pereira, Secolin Rodrigo, Santos Marilza L, Coan Ana Carolina, Vieira André S, Torres Fábio R, Carvalho Benilton S, Alvim Marina K M, Morita Márcia E, Yasuda Clarissa L, Pimentel-Silva Luciana R, Dogini Danyella B, Rogerio Fabio, Cendes Fernando, Lopes-Cendes Iscia
Department of Medical Genetics, University of Campinas - UNICAMP, and the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil.
Department of Neurology, University of Campinas - UNICAMP, and the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil.
PLoS One. 2017 Apr 6;12(4):e0173060. doi: 10.1371/journal.pone.0173060. eCollection 2017.
Epilepsy is misdiagnosed in up to 25% of patients, leading to serious and long-lasting consequences. Recently, circulating microRNAs have emerged as potential biomarkers in a number of clinical scenarios. The purpose of this study was to identify and to validate circulating microRNAs that could be used as biomarkers in the diagnosis of epilepsy. Quantitative real-time PCR was used to measure plasma levels of three candidate microRNAs in two phases of study: an initial discovery phase with 14 patients with mesial temporal lobe epilepsy (MTLE), 13 with focal cortical dysplasia (FCD) and 16 controls; and a validation cohort constituted of an independent cohort of 65 patients with MTLE and 83 controls. We found hsa-miR-134 downregulated in patients with MTLE (p = 0.018) but not in patients with FCD, when compared to controls. Furthermore, hsa-miR-134 expression could be used to discriminate MTLE patients with an area under the curve (AUC) of 0.75. To further assess the robustness of hsa-miR-134 as a biomarker for MTLE, we studied an independent cohort of 65 patients with MTLE, 27 of whom MTLE patients were responsive to pharmacotherapy, and 38 patients were pharmacoresistant and 83 controls. We confirmed that hsa-miR-134 was significantly downregulated in the plasma of patients with MTLE when compared with controls (p < 0.001). In addition, hsa-miR-134 identified patients with MTLE regardless of their response to pharmacotherapy or the presence of MRI signs of hippocampal sclerosis. We revealed that decreased expression of hsa-miR-134 could be a potential non-invasive biomarker to support the diagnosis of patients with MTLE.
高达25%的患者癫痫被误诊，会导致严重且持久的后果。最近，循环微小RNA已成为多种临床情况下的潜在生物标志物。本研究的目的是鉴定和验证可作为癫痫诊断生物标志物的循环微小RNA。在研究的两个阶段中，采用定量实时PCR检测三种候选微小RNA的血浆水平：初始发现阶段，有14例内侧颞叶癫痫（MTLE）患者、13例局灶性皮质发育不良（FCD）患者和16例对照；验证队列由65例MTLE患者和83例对照的独立队列组成。与对照相比，我们发现MTLE患者中hsa-miR-134下调（p = 0.018），而FCD患者中未下调。此外，hsa-miR-134表达可用于区分MTLE患者，曲线下面积（AUC）为0.75。为了进一步评估hsa-miR-134作为MTLE生物标志物的稳健性，我们研究了一个独立队列，其中有65例MTLE患者，其中27例MTLE患者对药物治疗有反应，38例患者药物抵抗，以及83例对照。我们证实，与对照相比，MTLE患者血浆中hsa-miR-134显著下调（p < 0.001）。此外，无论对药物治疗的反应或海马硬化的MRI征象如何，hsa-miR-134均可识别MTLE患者。我们发现hsa-miR-134表达降低可能是支持MTLE患者诊断的潜在非侵入性生物标志物。
