Development of the correlation between mitophagy-related genes and epilepsy

Abstract

Abstract Background Approximately 30% of patients with epilepsy are refractory to medication. Dysregulation of mitochondrial autophagy in the central nervous system may be associated with the pathogenesis of epilepsy. Therefore, we conducted a global analysis to elucidate the biological roles of mitophagy-related genes in epilepsy. Methods We downloaded the GSE143272 dataset from the Gene Expression Omnibus (GEO) database and identified mitophagy-related genes (MRGs) from the Molecular Signatures Database. The differentially expressed MRGs between drug-naïve patients with epilepsy and healthy individuals were identified. A protein–protein interaction (PPI) network and diagnostic model were then constructed. Subsequently, we performed functional enrichment and clustering analysis to identify the different epilepsy subtypes. Weighted gene co-expression network analysis was used to identify significant modules closely related to epilepsy, and a PPI network was co-constructed with MRGs to obtain hub genes. Finally, we used CIBERSORT to further investigate the distribution pattern of peripheral blood immune cell subtypes in patients with epilepsy, as well as the correlation between hub genes, MRG expression, and immune cell infiltration. Results We identified 11 differentially expressed MRGs (5 upregulated and 6 downregulated). The MRG diagnostic model used in our study showed good diagnostic performance. We identified the top six significant modules that were closely related to epilepsy. By co-constructing PPI with MRGs, we obtained the top 10 hub genes and constructed a competing endogenous RNA (ceRNA) network. Furthermore, CIBERSORT analysis indicated that patients with epilepsy had a higher infiltration level of neutrophils, and the hub genes and differentially expressed MRGs were highly correlated with infiltrating immune cells. Conclusions Our findings highlight that mitophagy is associated with epilepsy and may provide a novel direction for the diagnosis and treatment of the disease.