Dual-center, dual-platform microRNA profiling identifies potential plasma biomarkers of adult temporal lobe epilepsy

  • Background: There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable detection in biofluids. Altered levels of circulating microRNAs have been reported in human epilepsy, but most studies collected samples from one clinical site, used a single profiling platform or conducted minimal validation. Method: Using a case-control design, we collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated findings in a large (>250) cohort of samples that included patients with psychogenic non-epileptic seizures (PNES). Findings: After profiling and validation, we identified miR-27a-3p, miR-328-3p and miR-654-3p with biomarker potential. Plasma levels of these microRNAs were also changed in a mouse model of TLE but were not different to healthy controls in PNES patients. We determined copy number of the three microRNAs in plasma and demonstrate their rapid detection using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Analysis of the microRNAs within the exosome-enriched fraction provided high diagnostic accuracy while Argonaute-bound miR-328-3p selectively increased in patient samples after seizures. In situ hybridization localized miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics predicted targets linked to growth factor signaling and apoptosis. Interpretation: This study demonstrates the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms.
Author:Rana Raoof, Sebastian BauerORCiDGND, Hany El Naggar, Niamh M. C. ConnollyORCiD, Gary P. BrennanORCiD, Elizabeth Brindley, Thomas Hill, Hazel McArdle, Elaine Spain, Robert J. Forster, Jochen H. M. PrehnORCiD, Hajo Hamer, Norman Delanty, Felix RosenowORCiDGND, Catherine Mooney, David C. HenshallORCiD
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30396857
Parent Title (English):EBioMedicine
Place of publication:Amsterdam [u. a.]
Document Type:Article
Year of Completion:2018
Date of first Publication:2018/11/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/04/23
Tag:Biofluids; Dissociative seizures; Noncoding RNA; Serum; Status epilepticus; Temporal lobe epilepsy
Page Number:15
First Page:127
Last Page:141
© 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0