Higher vascularity at infiltrated peripheral edema differentiates proneural glioblastoma subtype

PLoS One. 2020 Oct 14;15(10):e0232500. doi: 10.1371/journal.pone.0232500. eCollection 2020.

Abstract

Background and purpose: Genetic classifications are crucial for understanding the heterogeneity of glioblastoma. Recently, perfusion MRI techniques have demonstrated associations molecular alterations. In this work, we investigated whether perfusion markers within infiltrated peripheral edema were associated with proneural, mesenchymal, classical and neural subtypes.

Materials and methods: ONCOhabitats open web services were used to obtain the cerebral blood volume at the infiltrated peripheral edema for MRI studies of 50 glioblastoma patients from The Cancer Imaging Archive: TCGA-GBM. ANOVA and Kruskal-Wallis tests were carried out in order to assess the association between vascular features and the Verhaak subtypes. For assessing specific differences, Mann-Whitney U-test was conducted. Finally, the association of overall survival with molecular and vascular features was assessed using univariate and multivariate Cox models.

Results: ANOVA and Kruskal-Wallis tests for the maximum cerebral blood volume at the infiltrated peripheral edema between the four subclasses yielded false discovery rate corrected p-values of <0.001 and 0.02, respectively. This vascular feature was significantly higher (p = 0.0043) in proneural patients compared to the rest of the subtypes while conducting Mann-Whitney U-test. The multivariate Cox model pointed to redundant information provided by vascular features at the peripheral edema and proneural subtype when analyzing overall survival.

Conclusions: Higher relative cerebral blood volume at infiltrated peripheral edema is associated with proneural glioblastoma subtype suggesting underlying vascular behavior related to molecular composition in that area.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Edema / diagnostic imaging
  • Brain Edema / physiopathology*
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / physiopathology
  • Cerebral Blood Volume
  • Female
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / physiopathology
  • Humans
  • Magnetic Resonance Angiography / methods*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Survival Analysis
  • Young Adult

Grants and funding

This work was partially supported by: MTS4up project (National Plan for Scientific and Technical Research and Innovation 2013-2016, No. DPI2016-80054-R) (JMGG); H2020-SC1-2016-CNECT Project (No. 727560) (JMGG), Fundació Bancaria laCaixa (LCF/TR/CI16/10010016) and H2020-SC1-BHC-2018-2020 (No. 825750) (JMGG); PID2019-104978RB-I00 (Ministerio de Ciencia e Innovación) (JMGG). MAT was supported by DPI2016-80054-R (Programa Estatal de Promoción del Talento y su Empleabilidad en I+D+i). EFG was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 844646. There was no additional external funding received for this study.