The Important Role of Perituberal Tissue in Epileptic Patients with Tuberous Sclerosis Complex by the Transcriptome Analysis

Epilepsy is most common in patients with tuberous sclerosis complex (TSC). However, in addition to the challenging treatment, the pathogenesis of epilepsy is still controversial. To determine the transcriptome characteristics of perituberal tissue (PT) and clarify its role in the pathogenesis of epilepsy, GSE16969 was downloaded from the GEO database for further study by comprehensive bioinformatics analysis. Identification of differentially expressed genes (DEGs), functional enrichment analysis, construction of protein-protein interaction (PPI) network, and selection of Hub genes were performed using R language, Metascape, STRING, and Cytoscape, respectively. Comparing with cortical tuber (CT), 220 DEGs, including 95 upregulated and 125 downregulated genes, were identified in PT and mainly enriched in collagen-containing extracellular matrix and positive regulation of receptor-mediated endocytosis, as well as the pathways of ECM-receptor interaction and neuroactive ligand-receptor interaction. As for normal cortex (NC), 1549 DEGs, including 30 upregulated and 1519 downregulated genes, were identified and mainly enriched in presynapse, dendrite and axon, and also the pathways of dopaminergic synapse and oxytocin signaling pathway. In the PPI network, 4 hub modules were found between PT and CT, and top 5 hub modules were selected between PT and NC. C3, APLNR, ANXA2, CD44, CLU, CP, MCHR2, HTR1E, CTSG, APP, and GNG2 were identified as Hub genes, of which, C3, CD44, ANXA2, HTR1E, and APP were identified as Hub-BottleNeck genes. In conclusion, PT has the unique characteristics different from CT and NC in transcriptome and makes us further understand its importance in the TSC-associated epilepsy.