10779/rcsi.10790735.v1
Rana Raoof
Rana
Raoof
Sebastian Bauer
Sebastian
Bauer
Hany El Naggar
Hany El
Naggar
Gary P Brennan
Gary P
Brennan
Elizabeth Brindley
Elizabeth
Brindley
Thomas Hill
Thomas
Hill
Hazel McArdle
Hazel
McArdle
Elaine Spain
Elaine
Spain
Robert J Forster
Robert J
Forster
Jochen HM Prehn
Jochen HM
Prehn
Hajo Hamer
Hajo
Hamer
Norman Delanty
Norman
Delanty
Felix Rosenow
Felix
Rosenow
Catherine Mooney
Catherine
Mooney
David C. Henshall
David C.
Henshall
Dual-center, dual-platform microRNA profiling identifies potential plasma biomarkers of adult temporal lobe epilepsy.
Royal College of Surgeons in Ireland
2019
Animals
Biomarkers
Case-Control Studies
Circulating MicroRNA
Computational Biology
Disease Models
Animal
Epilepsy
Temporal Lobe
Gene Expression Profiling
Gene Regulatory Networks
High-Throughput Nucleotide Sequencing
Humans
Mice
MicroRNAs
Transcriptome
Physiology
Medical Physics
2019-11-22 16:56:28
Journal contribution
https://repository.rcsi.com/articles/journal_contribution/Dual-center_dual-platform_microRNA_profiling_identifies_potential_plasma_biomarkers_of_adult_temporal_lobe_epilepsy_/10790735
<p>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.</p>
<p>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).</p>
<p>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.</p>
<p>INTERPRETATION: This study demonstrates the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms.</p>