# Molecular Signature in Focal Cortical Dysplasia: A Systematic Review of RNA and Protein Data

## TL;DR

This study reviews RNA and protein data to identify shared molecular patterns in focal cortical dysplasia, offering insights into potential treatments.

## Contribution

The paper presents the first cross-omics molecular framework for FCD, unifying heterogeneous findings and guiding biomarker discovery.

## Key findings

- Convergent dysregulation of neuroinflammatory, synaptic, cytoskeletal, and metabolic pathways was found across FCD subtypes.
- Consistently altered genes and microRNAs were linked to key signaling pathways like PI3K–Akt–mTOR and Toll-like receptor.
- Overlapping transcript–protein patterns and subtype-specific profiles were identified for improved diagnosis and therapy.

## Abstract

Focal cortical dysplasia (FCD) is a major cause of drug-resistant epilepsy, yet its molecular basis remains poorly understood. Numerous studies have analyzed RNA, protein, and microRNA alterations, but results are often inconsistent across subtypes and methodologies. To address this gap, we conducted a systematic review integrating transcriptomic, proteomic, and microRNA data from 117 human studies of FCD subtypes I–III. Differentially expressed factors were extracted, categorized by subtype, and analyzed using pathway enrichment and network approaches. Our integrative analysis revealed convergent dysregulation of neuroinflammatory, synaptic, cytoskeletal, and metabolic pathways across FCD subtypes. Consistently altered genes, including IL1B, TLR4, BDNF, HMGCR, and ROCK2, together with dysregulated microRNAs such as hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-132-3p, were linked to PI3K–Akt–mTOR, Toll-like receptor, and GABAergic signaling, emphasizing shared pathogenic mechanisms. Importantly, we identified overlapping transcript–protein patterns and subtype-specific molecular profiles that may refine diagnosis and inform therapeutic strategies. This review provides the first cross-omics molecular framework of FCD, demonstrating how convergent pathways unify heterogeneous findings and offering a roadmap for biomarker discovery and targeted interventions.