Identification and validation of diagnostic biomarkers for temporal lobe epilepsy related to ferroptosis and potential therapeutic targets.

Ferroptosis pathway activation is potentially correlated with temporal lobe epilepsy (TLE). However, the diagnostic significance and mechanism of ferroptosis-related genes (FRGs) in TLE require further investigation. A comprehensive analysis of the GSE134697 dataset from the Gene Expression Omnibus (GEO) database using Weighted gene co-expression network analysis (WGCNA) identified 3,212 differentially expressed genes (DEGs) between temporal lobe epilepsy (TLE) and control groups, with a critical focus on the turquoise module. Through intersection of DEGs and key module genes, correlation analyses with functional-related genes (FRG), protein-protein interactions (PPI), least absolute shrinkage and selection operator (LASSO), and machine learning methods, five potential biomarkers of ferroptosis (CBS, SHMT1, RIN3, QDPR, and PLPP4) were isolated. A nomogram was constructed using these markers, and enrichment analyses revealed their links to T-cell activation, allograft rejection, and glial differentiation. Variations in 13 immune cell types were also noted. Upregulation of CBS, RIN3, QDPR, and PLPP4 in TLE was confirmed through RT-qPCR and Western blot assays. Additionally, five SHMT1-targeting and one CBS-targeting drugs were predicted using the Drug-Gene Interaction Database (DGIdb). These findings provide new insights into the potential pathogenesis of TLE and suggest new targets for future research.