Spatial transcriptome analysis reveals Notch pathway-associated prognostic markers in IDH1 wild-type glioblastoma involving the subventricular zone.
IF: 11.150
Cited by: 25


The spatial relationship of glioblastoma (GBM) to the subventricular zone (SVZ) is associated with inferior patient survival. However, the underlying molecular phenotype is largely unknown. We interrogated an SVZ-dependent transcriptome and potential location-specific prognostic markers. mRNA microarray data of a discovery set (n = 36 GBMs) were analyzed for SVZ-dependent gene expression and process networks using the MetaCore™ workflow. Differential gene expression was confirmed by qPCR in a validation set of 142 IDH1 wild-type GBMs that was also used for survival analysis. Microarray analysis revealed a transcriptome distinctive of SVZ+ GBM that was enriched for genes associated with Notch signaling. No overlap was found to The Cancer Genome Atlas's molecular subtypes. Independent validation of SVZ-dependent expression confirmed four genes with simultaneous prognostic impact: overexpression of HES4 (p = 0.034; HR 1.55) and DLL3 (p = 0.017; HR 1.61) predicted inferior, and overexpression of NTRK2 (p = 0.049; HR 0.66) and PIR (p = 0.025; HR 0.62) superior overall survival (OS). Additionally, overexpression of DLL3 was predictive of shorter progression-free survival (PFS) (p = 0.043; HR 1.64). Multivariate analysis revealed overexpression of HES4 to be independently associated with inferior OS (p = 0.033; HR 2.03), and overexpression of DLL3 with inferior PFS (p = 0.046; HR 1.65). We identified four genes with SVZ-dependent expression and prognostic significance, among those HES4 and DLL3 as part of Notch signaling, suggesting further evaluation of location-tailored targeted therapies.


Location-dependent prognostic markers
Notch signaling
Subventricular zone
mRNA microarray analysis

MeSH terms

Biomarkers, Tumor
Brain Neoplasms
Disease-Free Survival
Gene Expression Regulation, Neoplastic
Isocitrate Dehydrogenase
Lateral Ventricles
Middle Aged
RNA, Messenger
Receptors, Notch
Signal Transduction


Jungk, Christine
Mock, Andreas
Exner, Janina
Geisenberger, Christoph
Warta, Rolf
Capper, David
Abdollahi, Amir
Friauf, Sara
Lahrmann, Bernd
Grabe, Niels
Beckhove, Philipp
von Deimling, Andreas
Unterberg, Andreas
Herold-Mende, Christel

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