Circulating MicroRNAs From Plasma Small Extracellular Vesicles as Potential Diagnostic Biomarkers in Pediatric Epilepsy and Drug-Resistant Epilepsy

Yilong Wang; Yeping Wang; Yi Chen; Yi Hua; Lu Xu; Mengying Zhu; Congying Zhao; Weiran Zhang; Guoxia Sheng; Liu Liu; Peifang Jiang; Zhefeng Yuan; Zhengyan Zhao; Feng Gao

doi:10.3389/fnmol.2022.823802

Circulating MicroRNAs From Plasma Small Extracellular Vesicles as Potential Diagnostic Biomarkers in Pediatric Epilepsy and Drug-Resistant Epilepsy

Front Mol Neurosci. 2022 Feb 10:15:823802. doi: 10.3389/fnmol.2022.823802. eCollection 2022.

Authors

Yilong Wang^{1

2

3}, Yeping Wang^{1

2

3}, Yi Chen^{2

3}, Yi Hua^{1

2

3}, Lu Xu^{1

2

3}, Mengying Zhu^{2

3}, Congying Zhao^{1

2

3}, Weiran Zhang^{1

2

3}, Guoxia Sheng^{1

2

3}, Liu Liu^{1

2

3}, Peifang Jiang^{1

2

3}, Zhefeng Yuan^{1

2

3}, Zhengyan Zhao^{2

3}, Feng Gao^{1

2

3}

Affiliations

¹ Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ National Clinical Research Center for Child Health, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

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.

Keywords: anti-epileptic drug resistance; anti-epileptic drug response; epilepsy; microRNAs; small extracellular vesicle.