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

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.