Wang Jun, Tan Lan, Tan Lin, Tian Yan, Ma Jing, Tan Chen-Chen, Wang Hui-Fu, Liu Ying, Tan Meng-Shan, Jiang Teng, Yu Jin-Tai
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
Sci Rep. 2015 May 18;5:10201. doi: 10.1038/srep10201.
MicroRNAs (miRNAs) open up a new field for molecular diagnosis for cancer and other diseases based on their stability in serum. However, the role of circulating miRNAs in plasma/serum in epilepsy diagnosis is still unclear. The aim of this study was to evaluate whether miRNAs can be used as biomarkers for drug-resistant epilepsy. We measured the differences in serum miRNA levels between 30 drug-resistant patients and 30 drug-responsive epilepsy patients in discovery and training phases using Illumina HiSeq2000 sequencing followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays. The selected miRNAs were then validated in 77 drug-resistant epilepsy patients, 81 drug-responsive epilepsy patients and 85 healthy controls by qRT-PCR. We found that circulating miRNAs are differentially expressed between drug-resistant group and drug-responsive group. MiR-194-5p, -301a-3p, -30b-5p, -342-5p and -4446-3p were significantly deregulated in drug-resistant group compared to drug-responsive group and control group. Among these 5 miRNAs, miR-301a-3p had the best diagnostic value for drug-resistant epilepsy with 80.5% sensitivity and 81.2% specificity, and was negatively associated with seizure severity. These provide the rationale for further confirmation studies in larger prospective cohorts and in other ethnics.
微小RNA（miRNA）基于其在血清中的稳定性，为癌症和其他疾病的分子诊断开辟了一个新领域。然而，循环miRNA在血浆/血清中对癫痫诊断的作用仍不清楚。本研究的目的是评估miRNA是否可作为耐药性癫痫的生物标志物。我们在发现阶段和训练阶段，使用Illumina HiSeq2000测序，随后进行定量逆转录聚合酶链反应（qRT-PCR）分析，测量了30例耐药患者和30例药物反应性癫痫患者血清miRNA水平的差异。然后，通过qRT-PCR在77例耐药性癫痫患者、81例药物反应性癫痫患者和85例健康对照中对所选miRNA进行验证。我们发现，耐药组和药物反应组之间循环miRNA存在差异表达。与药物反应组和对照组相比，miR-194-5p、-301a-3p、-30b-5p、-342-5p和-4446-3p在耐药组中显著失调。在这5种miRNA中，miR-301a-3p对耐药性癫痫具有最佳诊断价值，敏感性为80.5%，特异性为81.2%，且与癫痫发作严重程度呈负相关。这些结果为在更大的前瞻性队列和其他种族中进行进一步的验证研究提供了理论依据。
