Molecular differences between cerebral blood volume and vessel size in glioblastoma multiforme.
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.
Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany.
Dieter Henrik
DH
Heiland
Department of Neuroradiology, Medical Center University of Freiburg, Freiburg, Germany.|Department of Radiology, Kantonsspital, Medical Center Universtiy of Basel, Switzerland.
Theo
T
Demerath
Medical Physics, Department of Radiology, Medical Center University of Freiburg, Freiburg, Germany.
Elias
E
Kellner
Medical Physics, Department of Radiology, Medical Center University of Freiburg, Freiburg, Germany.
Valerij G
VG
Kiselev
Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center University of Freiburg, Freiburg, Germany.
Dietmar
D
Pfeifer
Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany.
Oliver
O
Schnell
Department of Neuropathology, Medical Center University of Freiburg, Freiburg, Germany.
Ori
O
Staszewski
Department of Neuroradiology, Medical Center University of Freiburg, Freiburg, Germany.
Horst
H
Urbach
Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany.
Astrid
A
Weyerbrock
Department of Neuroradiology, Medical Center University of Freiburg, Freiburg, Germany.
Irina
I
Mader
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000235:genetics*; D000071937:Cerebral Blood Volume / Q000235:genetics*; D016000:Cluster Analysis; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005909:Glioblastoma / Q000098:blood supply / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010477:Perfusion; D011446:Prospective Studies
D003287:Contrast Media
CBV; WGCNA; glioblastoma; radiogenomics; vessel size imaging