Adverse prognosis of glioblastoma contacting the subventricular zone: Biological correlates

Autoři: Sharon Berendsen aff001;  Emma van Bodegraven aff002;  Tatjana Seute aff001;  Wim G. M. Spliet aff003;  Marjolein Geurts aff001;  Jeroen Hendrikse aff004;  Laurent Schoysman aff005;  Willemijn B. Huiszoon aff001;  Meri Varkila aff001;  Soufyan Rouss aff001;  Erica H. Bell aff007;  Jérôme Kroonen aff001;  Arnab Chakravarti aff007;  Vincent Bours aff005;  Tom J. Snijders aff001;  Pierre A. Robe aff001
Působiště autorů: UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center of Utrecht, Utrecht, The Netherlands aff001;  UMC Utrecht Brain Center, Department of Translational Neuroscience, University Medical Center of Utrecht, Utrecht, The Netherlands aff002;  Department of Pathology, University Medical Center of Utrecht, Utrecht, The Netherlands aff003;  Department of Radiology, University Medical Center of Utrecht, Utrecht, The Netherlands aff004;  Department of Human Genetics, GIGA Research Center, Liège University Hospital, Liège, Belgium aff005;  Department of Radiology, Liège University Hospital, Liège, Belgium aff006;  Department of Radiation Oncology, Wexner Medical Center, James Cancer Center, Ohio State University, Columbus, OH, United States of America aff007
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article



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.


We analyzed T1-weighted, gadolinium-enhanced MR images of a retrospective cohort of 647 primary 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.


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.


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.

Klíčová slova:

Cancer treatment – Gene expression – Magnetic resonance imaging – MicroRNAs – Prognosis – Surgical and invasive medical procedures – Surgical oncology – Glioblastoma multiforme


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