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Background  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.    Methods  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.    Results  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).    Conclusions  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.    Electronic supplementary material  The online version of this article (doi:10.1186/s12916-016-0710-7) contains supplementary material, which is available to authorized users.

Spatial transcriptome analysis reveals Notch pathway-associated prognostic markers in IDH1 wild-type glioblastoma involving the subventricular zone