%0 Journal Article
%@ 1741-7015
%A Jungk, Christine
%A Mock, Andreas
%A Exner, Janina
%A Geisenberger, Christoph
%A Warta, Rolf
%A Capper, David
%A Abdollahi, Amir
%A Friauf, Sara
%A Lahrmann, Bernd
%A Grabe, Niels
%A Beckhove, Philipp
%A von Deimling, Andreas
%A Unterberg, Andreas
%A Herold-Mende, Christel
%C London; Berlin; Heidelberg
%D 2016
%F heidok:22044
%I BioMed Central; Springer
%J BMC Medicine
%N 170
%P 1-16
%R http://dx.doi.org/10.1186/s12916-016-0710-7
%T Spatial transcriptome analysis reveals Notch pathway-associated prognostic markers in IDH1 wild-type glioblastoma involving the subventricular zone
%U https://archiv.ub.uni-heidelberg.de/volltextserver/22044/
%V 14
%X 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.