Adverse prognosis of glioblastoma contacting the subventricular zone: Biological correlates
Berendsen, Sharon; van Bodegraven, Emma; Seute, Tatjana; Spliet, Wim G M; Geurts, Marjolein; Hendrikse, Jeroen; Schoysman, Laurent; Huiszoon, Willemijn B; Varkila, Meri; Rouss, Soufyan; Bell, Erica H; Kroonen, Jérôme; Chakravarti, Arnab; Bours, Vincent; Snijders, Tom J; Robe, Pierre A
(2019) PLoS ONE, volume 14, issue 10, pp. 1 - 16
(Article)
Abstract
INTRODUCTION: The subventricular zone (SVZ) in the brain is associated with gliomagenesis and resistance to treatment in glioblastoma. In this study, we investigate the prognostic role and biological characteristics of subventricular zone (SVZ) involvement in glioblastoma. METHODS: We analyzed T1-weighted, gadolinium-enhanced MR images of a retrospective cohort of 647 primary
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glioblastoma patients diagnosed between 2005-2013, and performed a multivariable Cox regression analysis to adjust the prognostic effect of SVZ involvement for clinical patient- and tumor-related factors. Protein expression patterns of a.o. markers of neural stem cellness (CD133 and GFAP-δ) and (epithelial-) mesenchymal transition (NF-κB, C/EBP-β and STAT3) were determined with immunohistochemistry on tissue microarrays containing 220 of the tumors. Molecular classification and mRNA expression-based gene set enrichment analyses, miRNA expression and SNP copy number analyses were performed on fresh frozen tissue obtained from 76 tumors. Confirmatory analyses were performed on glioblastoma TCGA/TCIA data. RESULTS: Involvement of the SVZ was a significant adverse prognostic factor in glioblastoma, independent of age, KPS, surgery type and postoperative treatment. Tumor volume and postoperative complications did not explain this prognostic effect. SVZ contact was associated with increased nuclear expression of the (epithelial-) mesenchymal transition markers C/EBP-β and phospho-STAT3. SVZ contact was not associated with molecular subtype, distinct gene expression patterns, or markers of stem cellness. Our main findings were confirmed in a cohort of 229 TCGA/TCIA glioblastomas. CONCLUSION: In conclusion, involvement of the SVZ is an independent prognostic factor in glioblastoma, and associates with increased expression of key markers of (epithelial-) mesenchymal transformation, but does not correlate with stem cellness, molecular subtype, or specific (mi)RNA expression patterns.
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Keywords: General Biochemistry,Genetics and Molecular Biology, General Agricultural and Biological Sciences, General
ISSN: 1932-6203
Publisher: Public Library of Science
Note: Funding Information: This work was supported by the following grants: PNC-029-006 of the Belgian Ministry of Health, grants FRSM 3.4.562.12, Televie 1.5.162.10 of the FNRS of Belgium, FBC 2010.14 of the Belgian Foundation against Cancer, and an unrestricted grant of the TandP Bohnenn fund for Neuro-Oncological Research to TS and PR. In addition, this work was supported by National Cancer Institute R01CA169368, R01CA108633, R01CA188228, R01CA188500, 1RC2CA148190 and The Ohio State University Comprehensive Cancer Center Award (all to A.C.). We also thank The Ohio State University (OSU) Comprehensive Cancer Center Genomics Shared Resource supported in part by grant P30 CA016058, National Cancer Institute, Bethesda, MD Publisher Copyright: © 2019 Berendsen et al. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
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