Abstract
Pediatric epilepsy is a neurological condition that causes repeated and unprovoked seizures and is more common in 1–5-year-old children. Drug resistance has been indicated as a key challenge in improving the clinical outcomes of patients with pediatric epilepsy. In the present study, we aimed to identify plasma small extracellular vesicles (sEVs) derived microRNAs (miRNAs) from the plasma samples of children for predicting the prognosis in patients with epilepsy and drug-resistant epilepsy. A total of 90 children clinically diagnosed with epilepsy [46 antiepileptic drug (AED)-responsive epilepsy and 44 drug-resistant epilepsy] and 37 healthy controls (HCs) were enrolled in this study. RNA sequencing was performed to identify plasma sEVs derived miRNAs isolated from the children’s plasma samples. Differentially expressed plasma sEVs derived miRNAs were identified using bioinformatics tools and were further validated by reverse transcription-polymerase chain reaction and receiver operator characteristic (ROC) curve analysis. In the present study, 6 miRNAs (hsa-miR-125b-5p, hsa-miR-150-3p, hsa-miR-199a-3p, hsa-miR-584-5p hsa-miR-199a-5p, and hsa-miR-342-5p) were selected for further validation. hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-150-5p with area under curve (AUC) values of 0.846, 0.835, and 0.826, respectively, were identified as promising biomarkers of epilepsy. A logistic model combining three miRNAs (hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-199a-3p) could achieve an AUC of 0.883 and a six miRNAs model (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) could attain an AUC of 0.888. The predicted probability of multiple miRNA panels was evaluated for differentiating between drug-resistant children and drug-responsive children. The AUC of a six-miRNA panel (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) reached 0.823. We identified and confirmed plasma sEVs derived miRNA biomarkers that could be considered as potential therapeutic targets for pediatric epilepsy and drug-resistant epilepsy.
Highlights
Epilepsy is a serious neurological disease affecting the development of children and their quality of life and having an incidence rate of 33/100,000–82/100,000 cases per year (Plevin and Smith, 2019)
No study or clinical trial has been reported on AEDs that can regulate the pathophysiology of seizure suppression, and no biomarkers are available for predicting the response to specific antiepileptic drugs (BarkerHaliski et al, 2015; Ma, 2018)
The total RNA products were reverse-transcribed into complementary DNA by PrimeScriptTM Reverse transcription (RT) reagent Kit (Perfect Real Time) (TAKARA, RR037A)
Summary
Epilepsy is a serious neurological disease affecting the development of children and their quality of life and having an incidence rate of 33/100,000–82/100,000 cases per year (Plevin and Smith, 2019). Techniques, including neuroimaging and electroencephalography (EEG), contribute to optimizing the classification (Scheffer et al, 2017) Multiple factors such as environmental factors and gene mutations are considered to contribute to epilepsy; the traditional classification of epilepsy based on clinical and neurological history, EEG, and neuroimaging is not sufficient to elucidate its pathogenesis and epileptogenesis (Manford, 2017). Several new antiepileptic drugs have been approved for children with epilepsy, the incidence rate of drug-resistant epilepsy (DRE) has not been decreased (Li et al, 2013). Invasive biomarkers for DRE diagnosis can effectively facilitate disease-related treatment and improve the quality of life
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