Title |
Spatial transcriptome analysis reveals Notch pathway-associated prognostic markers in IDH1 wild-type glioblastoma involving the subventricular zone
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Published in |
BMC Medicine, October 2016
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DOI | 10.1186/s12916-016-0710-7 |
Pubmed ID | |
Authors |
Christine Jungk, Andreas Mock, Janina Exner, Christoph Geisenberger, Rolf Warta, David Capper, Amir Abdollahi, Sara Friauf, Bernd Lahrmann, Niels Grabe, Philipp Beckhove, Andreas von Deimling, Andreas Unterberg, Christel Herold-Mende |
Abstract |
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. |
X Demographics
Geographical breakdown
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 50% |
Scientists | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 52 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 9 | 17% |
Student > Ph. D. Student | 8 | 15% |
Researcher | 6 | 12% |
Student > Bachelor | 5 | 10% |
Student > Doctoral Student | 4 | 8% |
Other | 10 | 19% |
Unknown | 10 | 19% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 17 | 33% |
Biochemistry, Genetics and Molecular Biology | 10 | 19% |
Neuroscience | 7 | 13% |
Agricultural and Biological Sciences | 5 | 10% |
Immunology and Microbiology | 1 | 2% |
Other | 2 | 4% |
Unknown | 10 | 19% |