Serum MicroRNAs as Predictors of Diagnosis and Drug-resistance in Temporal Lobe Epilepsy: A Preliminary Study

Abstract

Objective: Temporal lobe epilepsy (TLE) is the most common form of refractory focal epilepsy, and the current clinical diagnosis is based on EEG, clinical neurological history and neuroimaging findings.

Methods: So far, there are no blood-based molecular biomarkers of TLE to support clinical diagnosis, despite the pathogenic mechanisms underlying TLE involving defects in the regulation of gene expression. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of gene expression.

Results: Recent studies show the feasibility of detecting miRNAs in body fluids; circulating miRNAs have emerged as potential clinical biomarkers in epilepsy, although the TLE miRNA profile needs to be addressed. Here, we analysed the diagnostic potential of 8 circulating miRNAs in sera of 52 TLE patients and 40 age- and sex-matched donor controls by RT-qPCR analyses.

Conclusion: We found that miR-34a-5p, -106b-5p, -130a-3p, -146a-5p, and -19a-3p are differently expressed in TLE compared to control subjects, suggesting a diagnostic role. Furthermore, we found that miR-34a-5p, -106b-5p, -146a-5p and miR-451a could become prognostic biomarkers, being differentially expressed between drug-resistant and drug-responsive TLE subjects. Therefore, serum miRNAs are diagnostic and drug-resistance predictive molecules of TLE.

Keywords: TLE; Temporal lobe epilepsy; circulating biomarkers.; diagnosis; miRNAs; microRNAs; prediction of therapy response; prognosis.

Fig. (1)

RT-qPCR analysis of 7 diagnostic serum miRNAs. Scattered plots represent miR-34a-5p (A), miR-106b-5p (B), miR-130a-3p (C), miR-146a-5p (D), miR-451 (E), Let-7d (F), miR-19b-3p (G) relative expression (2^-DCT) in Non-epileptic versus TLE epileptic patients (t-test, p-value < 0.05, *; <0.01,**; NS, not significant). Average values are indicated by the bar.

Fig. (2)

Analysis of miRNA predicted target. (A) Summary table of the predicted target mRNAs of upregulated miR34a-5p, miR-130a-3p, miR-146a-5p and miR-106b-5p. (B) Diagram representing common target mRNAs among miR-34a-5p, -130a-3p, -146a-5p, and -106b-5p in TLE.

Fig. (3)

Pathways enriched with miR-19b-3p targets. The size of the circles indicates the number of miRNA targets in that pathway. The colour of the circles shows the adjusted p-values.

Fig. (4)

Relative expression of 6 serum miRNAs predictors of AED response. Scattered plots represent miR-34a-5p (A), miR-106b-5p (B), miR-146a-5p (C), miR-451 (D), Let-7d (E), miR-19b-3p (F-G) expression in AEDs drug-responsive versus drug-resistant TLE subjects (t-test, p-value < 0.05,*; < 0.001,***). Average values are indicated by the bar.