Divergent and Shared Alterations of Notch Signalling in Human Epilepsy and Glioblastoma Publisher Pubmed

Summary: What links epilepsy and brain tumors? Gene-network analysis suggests Notch, immune and oxidative-stress pathways interact differently across brain diseases. #Epilepsy #Glioblastoma

Meshkinkhood N ; Ebrahimi S ; Alipour F ; Noorbakhsh F ; Ghadipasha M ; Gharehdaghi J ; Meuth S G ; Speckmann E J ; Stummer W ; Gorji A ; Khaleghi Ghadiri M
Source: Experimental Neurology Published:2027

Abstract

Epilepsy and glioblastoma (GBM) share pathological features including neuroinflammation, glial activation, and disrupted cellular homeostasis; however, their systems-level molecular organization remains poorly understood. This study investigated context-dependent alterations in Notch signalling, innate immune pathways, and oxidative stress responses across human control, epileptic, and GBM brain tissues. Differential expression, correlation, and co-expression network analyses were performed using qRT-PCR data, complemented by independent GTEx and GEO transcriptomic datasets. NOTCH1 expression was increased in both epilepsy and GBM, whereas NOTCH2 was elevated specifically in GBM. GFAP and IBA1 expression increased in epilepsy, while only IBA1 remained elevated in GBM. KI67 expression was markedly increased in GBM and modestly elevated in epilepsy, while NEUN expression was reduced in GBM. KEAP1, NRF2, JAG1, NLE1, and TLR4 showed no significant differences among groups, whereas TLR3 was selectively upregulated in GBM. Despite limited differential expression of oxidative stress-related transcripts, correlation analyses revealed substantial differences in gene–gene co-expression patterns. Epilepsy showed stronger co-expression relationships among Notch, immune, and glial markers, whereas GBM exhibited greater integration of Notch, oxidative stress, and inflammatory genes. Independent GTEx and GEO datasets broadly reproduced these major disease-associated co-expression patterns. These findings suggest distinct disease-associated co-expression patterns involving Notch signalling and inflammatory, glial, and oxidative stress pathways in epilepsy and GBM that may not be evident from differential expression alone. © 2026 The Authors