The Biomarkers and Underlying Mechanisms of Mitochondrial and Programmed Cell Death Related Genes in Epilepsy by Combining Transcriptome and Single-Cell Sequencing

다국어 초록 (Multilingual Abstract)

Objective : Reactive oxygen species generated by mitochondria contribute to the induction of programmed cell death (PCD), but their involvement in epilepsy remains uncertain. The present study investigates the biomarkers and underlying mechanisms of mitochondriarelated genes (MRGs) and PCD-related genes (PCDRGs) in epilepsy.
Methods : The MRGs and PCDRGs were respectively intersected with differentially expressed genes in epilepsy and control samples within the GSE134697. Afterwards, Spearman correlation analysis was implemented to select candidate genes. Thereafter, candidate biomarkers were identified through intersection of eight algorithm results in cytoHubba plugin. The receiver operating characteristic curve analysis and expression validation in GSE134697 and GSE168375 were implemented to select biomarkers. Moreover, functional analysis, drug prediction and molecular docking were carried out to explore the mechanism of biomarkers in epilepsy, as well as single cell RNA sequencing analysis. Finally, the expression of biomarkers in clinical sample was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Results : LTBR and IRF1 were down-regulated in epilepsy samples in both GSE134697 and GSE168375 datasets, Therefore, they were identified as biomarkers for epilepsy related to PCD and mitochondria. IRF1 formed a hydrogen bond interaction with the recombinant cytokine, indicating recombinant cytokine was an effective drug target, while LTBR was not a suitable drug target. The macrophage was observed to engage in more frequent and intensive interactions with other cells. RT-qPCR showed that both biomarkers also low expression in epilepsy clinical samples.
Conclusion : LTBR, IRF1 were identified as biomarkers associated with mitochondria and PCD in epilepsy, providing novel perspectives on the management of this condition.