title: Integrative Diffusion-Weighted Imaging and Radiogenomic Network Analysis of Glioblastoma multiforme.
abstract: In the past, changes of the Apparent Diffusion Coefficient in glioblastoma multiforme have been shown to be related to specific genes and described as being associated with survival. The purpose of this study was to investigate diffusion imaging parameters in combination with genome-wide expression data in order to obtain a comprehensive characterisation of the transcriptomic changes indicated by diffusion imaging parameters. Diffusion-weighted imaging, molecular and clinical data were collected prospectively in 21 patients. Before surgery, MRI diffusion metrics such as axial (AD), radial (RD), mean diffusivity (MD) and fractional anisotropy (FA) were assessed from the contrast enhancing tumour regions. Intraoperatively, tissue was sampled from the same areas using neuronavigation. Transcriptional data of the tissue samples was analysed by Weighted Gene Co-Expression Network Analysis (WGCNA) thus classifying genes into modules based on their network-based affiliations. Subsequent Gene Set Enrichment Analysis (GSEA) identified biological functions or pathways of the expression modules. Network analysis showed a strong association between FA and epithelial-to-mesenchymal-transition (EMT) pathway activation. Also, patients with high FA had a worse clinical outcome. MD correlated with neural function related genes and patients with high MD values had longer overall survival. In conclusion, FA and MD are associated with distinct molecular patterns and opposed clinical outcomes.
authors.affiliation: Department of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Dieter Henrik
authors.initials: DH
authors.lastname: Heiland
authors.affiliation: Department of Neuroradiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Carl Philipp
authors.initials: CP
authors.lastname: Simon-Gabriel
authors.affiliation: Department of Neuroradiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.|Department of Radiology, University of Basel, Basel, Switzerland.
authors.forename: Theo
authors.initials: T
authors.lastname: Demerath
authors.affiliation: Department of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Haaker
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.affiliation: Medical Physics, Department of Radiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Elias
authors.initials: E
authors.lastname: Kellner
authors.affiliation: Medical Physics, Department of Radiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Valerij G
authors.initials: VG
authors.lastname: Kiselev
authors.affiliation: Department of Neuropathology; Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Ori
authors.initials: O
authors.lastname: Staszewski
authors.affiliation: Department of Neuroradiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.affiliation: Department of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Weyerbrock
authors.affiliation: Department of Neuroradiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Mader
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019295:Computational Biology / Q000379:methods; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor