Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that have emerged as new potential epigenetic biomarkers. Here, we evaluate the efficacy of six circulating miRNA previously described in the literature as biomarkers for the diagnosis of temporal lobe epilepsy (TLE) and/or as predictive biomarkers to antiepileptic drug response. We measured the differences in serum miRNA levels by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays in a cohort of 27 patients (14 women and 13 men; mean ± SD age: 43.65 ± 17.07) with TLE compared to 20 healthy controls (HC) matched for sex, age and ethnicity (11 women and 9 men; mean ± SD age: 47.5 ± 9.1). Additionally, patients were classified according to whether they had drug-responsive (n = 17) or drug-resistant (n = 10) TLE. We have investigated any correlations between miRNAs and several electroclinical parameters. Three miRNAs (miR-142, miR-146a, miR-223) were significantly upregulated in patients (expressed as average expression ± SD). In detail, miR-142 expression was 0.40 ± 0.29 vs. 0.16 ± 0.10 in TLE patients compared to HC (t-test, p < 0.01), miR-146a expression was 0.15 ± 0.11 vs. 0.07 ± 0.04 (t-test, p < 0.05), and miR-223 expression was 6.21 ± 3.65 vs. 1.23 ± 0.84 (t-test, p < 0.001). Moreover, results obtained from a logistic regression model showed the good performance of miR-142 and miR-223 in distinguishing drug-sensitive vs. drug-resistant TLE. The results of this pilot study give evidence that miRNAs are suitable targets in TLE and offer the rationale for further confirmation studies in larger epilepsy cohorts.
Highlights
Temporal lobe epilepsy (TLE) is the most common form of drug-resistant focal epilepsy, and it is considered a network disorder involving widespread structural alterations beyond the putative epileptic focus [1,2]
Considering that few studies have examined correlations between miRNA and TLE, the objectives of this study are (i) to determine if changes in expression of six epilepsy-related miRNAs, namely, miR-146a-5p, miR-142-5p, miR-132-3p, miR-138-5p, miR-298, and miR-223-3p, are present in the serum of a TLE cohort, and (ii) to verify if the serum levels of these miRNAs are potentially associated with failure of antiseizure medications (ASMs)
All patients were on mono or polytherapy ASMs at their last clinical visit
Summary
Temporal lobe epilepsy (TLE) is the most common form of drug-resistant focal epilepsy, and it is considered a network disorder involving widespread structural alterations beyond the putative epileptic focus [1,2]. The pathological mechanism underlying TLE may involve abnormal gene expression regulation, including post-transcriptional networks. MiRNAs can be detected in blood and serum, making them suitable candidates as potential circulating biomarkers to assess disease risk and treatment responses. The identification of circulating biomarkers for resistant epilepsy could potentially improve the choice of correct treatment as well as the prognosis of epileptic patients. Many circulating miRNAs have been reported as differentially expressed in hippocampi and peripheral blood from both animal models and patients with temporal lobe epilepsy compared to nonepileptic subjects [13,14,15,16]. To perform this part of the study, we selected TLE patients who showed no response to at least two different ASM therapies
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