Protein Biomarker in Focal Cortical Dysplasia: Molecular Clues to Pathogenesis
Focal Cortical Dysplasia (FCD) is a major cause of drug-resistant epilepsy (DRE), particularly in pediatric and young adult populations characterized by structural abnormalities in cortical development. This study investigated 60 patients with histologically confirmed FCD, combining clinical, histopathological, and molecular data to identify subtype-specific molecular signatures. we investigated a panel of candidate protein biomarkers (AKT, PTEN, mTOR, HTR6, RHEB, KCNT1, RALA, DEPDC5) across FCD subtypes using patient-derived tissue samples. Our results reveal subtype-specific alterations in biomarker expression, particularly within the mTOR signaling pathway, supporting its central role in cortical malformations. Key dysregulated genes AKT, mTOR, PTEN, RHEB, DEPDC5, KCNT1, RALA, and HTR6 involved in mTOR signaling, neuronal excitability, and cortical development. Western blotting and IHC revealed marked upregulation of AKT and mTOR in FCD III, consistent with mTOR pathway hyperactivation. In contrast, KCNT1, RALA, and DEPDC5 were significantly downregulated across all subtypes, suggesting disrupted inhibitory signaling and GATOR1 complex dysfunction. ELISA assays validated increased expression of AKT, mTOR, and HTR6, particularly in higher-grade lesions. This study bridges clinical, histopathological, and protein-level data, providing novel insight into the molecular basis of FCD and highlighting candidate biomarkers for future diagnostic and therapeutic applications