Expression of microRNA-129-2-3p and microRNA-935 in plasma and brain tissue of human refractory epilepsy.
Numerous microRNAs (miRNAs) are differentially expressed in specific diseases, suggesting possible use as diagnostic or prognostic biomarkers. The purpose of this study is to investigate the expression levels of miR-129-2-3p and miR-935 in cortical brain tissue and plasma samples from controls and refractory temporal lobe epilepsy (TLE) patients to evaluate the utility of these measures as diagnostic biomarkers.



The study was divided into three phases. First, cortical brain tissue samples from nine refractory TLE patients and eight controls were screened for differential miRNA expression using the Affymetrix miRNA 4.0 microarray. Second, real-time quantitative PCR (qRT-PCR) was used to verify the microarray results in brain tissue samples from 13 refractory TLE patients and 13 healthy controls (including those studied by microarray analysis). Third, we tested the expression levels of selected miRNAs in plasma samples from 25 refractory TLE patients and 25 healthy volunteers by qRT-PCR. The capacity of miR-129-2-3p and miR-935 expression to distinguish refractory TLE from health controls was tested by receiver operator characteristics (ROC) curve analysis.



(1) High-resolution miRNA arrays indicated that miR-129-2-3p and miR-935 were significantly upregulated in the cortical brain tissues of TLE patients compared to controls. (2) qRT-PCR confirmed upregulated miR-129-2-3p expression in the brain tissue(P<0.0001) and plasma samples(P=0.0008) of refractory TLE patients. (3) The expression of miR-935 in epilepsy patients was higher than control group, however, there are no significant statistical differences between them whether in plasma samples(P=0.644) or in tissue samples(P=0.258). (4) ROC analysis of miRNA-129-2-3p showed that the area under the curve (AUC) was 0.929 (95% CI: 0.833-1.000; p=0.000) for brain tissue and 0.778 (95% CI: 0.640-0.915; p=0.001) for plasma.



Expression of miRNA-129-2-3p was upregulated in cortical brain tissue and plasma samples from patients with refractory TLE, but miR-935 not. Plasma miRNA-129-2-3p has great potential as a non-invasive biomarker for early detection and clinical evaluation of refractory TLE.
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China; Department of Neurosurgery, Heilongjiang Provincial Hospital, Harbin, Heilongjiang, 150036, PR China.
Yuqiang
Y
Sun
Department of Neurosurgery, Weinan Central Hospital, Weinan, Shaanxi, 714000, PR China.
Xiaofeng
X
Wang
Department of Neurosurgery, Heilongjiang Provincial Hospital, Harbin, Heilongjiang, 150036, PR China.
Zeyang
Z
Wang
Department of Ultrasonography, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, PR China.
Yuanyang
Y
Zhang
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China.
Ningwei
N
Che
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China.
Xiadong
X
Luo
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China.
Zeshi
Z
Tan
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China.
Xu
X
Sun
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China.
Xinyu
X
Li
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China.
Kang
K
Yang
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China.
Guanyu
G
Wang
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China.
Lan
L
Luan
Department of Neurosurgery, Affiliated Fuxing Hospital, The Capital University of Medical Sciences, Beijing, 100038, PR China.
Yaoling
Y
Liu
Department of Neurosurgery and Pituiary Tumor Center, The Second Affiliated Hospital, SunYat-Sen University, Guangzhou, PR China.
Xiao
X
Zheng
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China.
Minghai
M
Wei
Department of Neurosurgery, Heilongjiang Provincial Hospital, Harbin, Heilongjiang, 150036, PR China. Electronic address: huakun_cheng@163.com.
Huakun
H
Cheng
Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China; Epileptic Center of Liaoning, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116044, PR China. Electronic address: syq_900309@163.com.
Jian
J
Yin
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000069279:Drug Resistant Epilepsy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
D015415:Biomarkers; C000608148:MIRN-935 microRNA, human; D035683:MicroRNAs; C541915:Mirn129 microRNA, human
Biomarker; MicroRNA; Plasma; Refractory epilepsy