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

Molecular Signature in Focal Cortical Dysplasia: A Systematic Review of RNA and Protein Data Data are available in interactive format (html) and could be downloaded in various formats through the file Deposited data: Protein dataset - Protein_fixed_doi mRNA dataset - RNA_fixed_doi miRNA dataset - miRNA_fixed_doi Abstract Focal cortical dysplasia (FCD) is a leading cause of drug-resistant epilepsy, but its molecular basis remains incompletely understood. This systematic review aimed to integrate findings from transcriptomic, proteomic, and microRNA studies across FCD subtypes (I–III) to identify convergent molecular signatures and potential pathogenic mechanisms. We conducted a comprehensive literature search and analysis of 117 studies that investigated differentially expressed microRNAs, mRNAs, and proteins in surgically resected human FCD tissue. Data were extracted, categorized by molecule type and FCD subtype, and evaluated for consistent dysregulation. Bioinformatics tools were used for pathway enrichment and miRNA–mRNA–protein network construction. We demonstrate convergent dysregulation of neuroinflammatory, synaptic, cytoskeletal, and metabolic pathways by merging molecular signals and subtypes (FCD I–III). Consistently altered genes and proteins, such as IL1B, TLR4, BDNF, HMGCR, and ROCK2, emphasize key nodes in FCD pathogenesis. Dysregulated microRNAs (e.g., hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-132-3p) were found to target immune, neuronal, and metabolic genes, with pathway analysis confirming their involvement in PI3K–Akt–mTOR, Toll-like receptor, and GABAergic signaling. Importantly, we identified overlapping transcript-protein patterns and constructed type-specific molecular profiles that may support precise diagnosis and future therapeutic targeting. This integrative review provides the first comprehensive molecular framework of FCD, demonstrating how converging molecular alterations shape disease mechanisms. The findings offer a foundation for biomarker discovery, mechanistic hypothesis generation, and the development of subtype-informed diagnostic and therapeutic strategies for FCD.