Jungk, Christine and Mock, Andreas and Exner, Janina and Geisenberger, Christoph and Warta, Rolf and Capper, David and Abdollahi, Amir and Friauf, Sara and Lahrmann, Bernd and Grabe, Niels and Beckhove, Philipp and von Deimling, Andreas and Unterberg, Andreas and Herold-Mende, Christel (2016) Spatial transcriptome analysis reveals Notch pathway-associated prognostic markers in IDH1 wild-type glioblastoma involving the subventricular zone. BMC MEDICINE, 14: 170. ISSN 1741-7015,
Full text not available from this repository. (Request a copy)Abstract
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 (TM) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEURAL STEM-CELLS; NEWLY-DIAGNOSED GLIOBLASTOMA; INITIATING CELLS; GENE-EXPRESSION; BREAST-CANCER; BRAIN-TUMORS; SURVIVAL; GLIOMA; MULTIFORME; GROWTH; Glioblastoma; Subventricular zone; mRNA microarray analysis; Location-dependent prognostic markers; Notch signaling |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Apr 2019 11:16 |
| Last Modified: | 24 Apr 2019 11:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4079 |
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