Towards molecular-guided epilepsy surgery: a systematic review and meta-analysis of microRNAs and other regulatory non-coding RNAs
Abstract
Non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and related species—have emerged as promising molecular biomarkers in epilepsy, but their diagnostic, prognostic, and therapeutic roles remain incompletely defined. We conducted a PRISMA 2020–compliant systematic review and meta-analysis (PROSPERO-registered). PubMed, Scopus, and Web of Science (2000–2025) were searched for studies evaluating ncRNA expression or clinical relevance in human epilepsy or validated animal models that reported diagnostic, prognostic, or treatment-response outcomes. Study quality was assessed with the Newcastle–Ottawa Scale, and pooled diagnostic estimates were generated when data allowed. Ninety-four studies met inclusion criteria: 79 investigated miRNAs, 10 lncRNAs, and several assessed piRNAs or circRNAs. The pooled area under the curve (AUC) for miRNA-based diagnostic models was 0.85, with mean sensitivity 76.5% and specificity 78.1%. lncRNAs showed a comparable mean AUC of 0.87, although based on fewer datasets. Recurrent biomarkers—particularly miR-134, miR-146a, and the lncRNA MALAT1—were consistently linked to drug-resistant epilepsy, higher seizure frequency, and poorer clinical control. Mechanistic analyses indicated that these ncRNAs regulate neuroinflammatory signaling, synaptic remodeling, and ion-channel–related pathways that are central to epileptogenesis. Overall, most studies were of moderate-to-high methodological quality. ncRNAs, especially…
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