Ventricular-Subventricular Zone Contact by Glioblastoma is Not Associated with Molecular Signatures in Bulk Tumor Data

Sci Rep. 2019 Feb 12;9(1):1842. doi: 10.1038/s41598-018-37734-w.


Whether patients with glioblastoma that contacts the ventricular-subventricular zone stem cell niche (VSVZ + GBM) have a distinct survival profile from VSVZ - GBM patients independent of other known predictors or molecular profiles is unclear. Using multivariate Cox analysis to adjust survival for widely-accepted predictors, hazard ratios (HRs) for overall (OS) and progression free (PFS) survival between VSVZ + GBM and VSVZ - GBM patients were calculated in 170 single-institution patients and 254 patients included in both The Cancer Genome (TCGA) and Imaging (TCIA) atlases. An adjusted, multivariable analysis revealed that VSVZ contact was independently associated with decreased survival in both datasets. TCGA molecular data analyses revealed that VSVZ contact by GBM was independent of mutational, DNA methylation, gene expression, and protein expression signatures in the bulk tumor. Therefore, while survival of GBM patients is independently stratified by VSVZ contact, with VSVZ + GBM patients displaying a poor prognosis, the VSVZ + GBMs do not possess a distinct molecular signature at the bulk sample level. Focused examination of the interplay between the VSVZ microenvironment and subsets of GBM cells proximal to this region is warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • DNA Methylation
  • Datasets as Topic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Humans
  • Lateral Ventricles / pathology*
  • Male
  • Stem Cell Niche / physiology*
  • Survival Analysis
  • Tumor Microenvironment