Oncotarget

Research Papers:

Molecular differences between cerebral blood volume and vessel size in glioblastoma multiforme

Dieter Henrik Heiland _, Theo Demerath, Elias Kellner, Valerij G. Kiselev, Dietmar Pfeifer, Oliver Schnell, Ori Staszewski, Horst Urbach, Astrid Weyerbrock and Irina Mader

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Oncotarget. 2017; 8:11083-11093. https://doi.org/10.18632/oncotarget.11522

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Abstract

Dieter Henrik Heiland1, Theo Demerath2,6, Elias Kellner3, Valerij G. Kiselev3, Dietmar Pfeifer4, Oliver Schnell1, Ori Staszewski5, Horst Urbach2, Astrid Weyerbrock1, Irina Mader2

1Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany

2Department of Neuroradiology, Medical Center University of Freiburg, Freiburg, Germany

3Medical Physics, Department of Radiology, Medical Center University of Freiburg, Freiburg, Germany

4Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center University of Freiburg, Freiburg, Germany

5Department of Neuropathology, Medical Center University of Freiburg, Freiburg, Germany

6Department of Radiology, Kantonsspital, Medical Center Universtiy of Basel, Switzerland

Correspondence to:

Dieter Henrik Heiland, email: [email protected]

Keywords: radiogenomics, CBV, vessel size imaging, WGCNA, glioblastoma

Received: April 27, 2016    Accepted: July 28, 2016    Published: August 23, 2016

ABSTRACT

The purpose of this study was to investigate the molecular background of cerebral blood volume (CBV) and vessel size (VS) of capillaries in glioblastoma multiforme (GBM). Both parameters are derived from extended perfusion MR imaging.

A prospective case study including 21 patients (median age 66 years, 10 females) was performed. Before operation, CBV and VS of contrast enhancing tumor were assessed. Tissue was sampled from the assessed areas under neuronavigation control. After RNA extraction, transcriptional data was analyzed by Weighted Gene Co-Expression Network Analysis (WGCNA) and split into modules based on its network affiliations. Gene Set Enrichment Analysis (GSEA) identified biological functions or pathways of the genetic modules. These were applied on 484 GBM samples of the TCGA database.

Ten modules were highly correlated to CBV and VS. One module was exclusively associated to VS and highly correlated to hypoxia, another one exclusively to CBV showing strong enrichments in the Epithelial Growth Factor (EGF) pathway and Epithelial-to-Mesenchymal-Transition (EMT). Moreover, patients with increased CBV and VS predominantly showed a mesenchymal gene-expression, a finding that could be corroborated by TCGA data.

In conclusion, CBV and VS mirror different genetic pathways and reflect certain molecular subclasses of GBM.


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