Identification of plasma SEMA3E as the diagnostic biomarker for human epilepsy based on integrated bioinformatics analysis

Despite advances in understanding epilepsy, challenges persist in identifying accessible and reliable biomarkers. In this study, an integrative analysis was conducted with transcriptomic data from both brain tissue and blood of epilepsy patients to identify common differentially expressed genes (DEGs). Using weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, and logistic regression, a robust epilepsy gene signature was constructed, and a hub gene associated with seizure frequency was identified. Single-cell RNA analysis, functional investigation, and clinical verification were subsequently conducted. Herein, we reported that the hub gene SEMA3E was significantly upregulated in both peripheral blood and epileptic brain tissue, with a positive correlation to seizure frequency. Subsequent analysis revealed that SEMA3E was enriched in excitatory neurons with NRP1 and VEGFR2, contributing to epileptogenesis by enhancing axonal growth. Clinical validation demonstrated that plasma SEMA3E levels were significantly elevated in epilepsy patients and correlated with specific clinical features. Unlike tissue biomarkers, blood-based SEMA3E exhibits advantages such as non-invasiveness and cost-effectiveness, making it suitable for large-scale screening and monitoring. This study highlights SEMA3E as a promising biomarker and therapeutic target for epilepsy, offering novel insights into its molecular and clinical relevance.