[en] 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 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Berendsen, S.; UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center of UtrechtUtrecht, Netherlands
van Bodegraven, E.; UMC Utrecht Brain Center, Department of Translational Neuroscience, University Medical Center of UtrechtUtrecht, Netherlands
Seute, T.; UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center of UtrechtUtrecht, Netherlands
Spliet, W. G. M.; Department of Pathology, University Medical Center of UtrechtUtrecht, Netherlands
Geurts, M.; UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center of UtrechtUtrecht, Netherlands
Hendrikse, J.; Department of Radiology, University Medical Center of UtrechtUtrecht, Netherlands
SCHOYSMAN, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > Département de Physique Médicale > Service médical de radiodiagnostic
Huiszoon, W. B.; UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center of UtrechtUtrecht, Netherlands
Varkila, M.; UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center of UtrechtUtrecht, Netherlands
Rouss, S.; UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center of UtrechtUtrecht, Netherlands
Bell, E. H.; Department of Radiation Oncology, Wexner Medical Center, James Cancer Center, Ohio State University, Columbus, OH, United States of America
Kroonen, J.; UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center of UtrechtUtrecht, Netherlands, Department of Human Genetics, GIGA Research Center, Liège University Hospital, Liège, Belgium
Chakravarti, A.; Department of Radiation Oncology, Wexner Medical Center, James Cancer Center, Ohio State University, Columbus, OH, United States of America
Bours, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique humaine
Snijders, T. J.; UMC Utrecht Brain Center, Department of Neurology and Neurosurgery, University Medical Center of UtrechtUtrecht, Netherlands
Robe, Pierre ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
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