radiogenomic mapping of edemacellular invasion mri-phenotypes in glioblastoma multiformeradiogenomic映射edemacellular入侵mri-phenotypes多形性成胶质细胞瘤.pdfVIP

Radiogenomic Mapping of Edema/Cellular Invasion MRI-Phenotypes in Glioblastoma Multiforme 1,2 3 1 1 1 Pascal O. Zinn *, Bhanu Majadan , Pratheesh Sathyan , Sanjay K. Singh , Sadhan Majumder , Ferenc A. 3 3 Jolesz , Rivka R. Colen * 1 Department of Genetics, M.D. Anderson Cancer Center, University of Texas, Houston, Texas, United States of America, 2 Department of Clinical Neurosciences, University Hospital (CHUV BH19-110), Lausanne, Switzerland, 3 Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America Abstract Background: Despite recent discoveries of new molecular targets and pathways, the search for an effective therapy for Glioblastoma Multiforme (GBM) continues. A newly emerged field, radiogenomics, links gene expression profiles with MRI phenotypes. MRI-FLAIR is a noninvasive diagnostic modality and was previously found to correlate with cellular invasion in GBM. Thus, our radiogenomic screen has the potential to reveal novel molecular determinants of invasion. Here, we present the first comprehensive radiogenomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expression profiling in GBM. Methods: Based on The Cancer Genome Atlas (TCGA), discovery and validation sets with gene, microRNA, and quantitative MR-imaging data were created. Top concordant genes and microRNAs correlated with high FLAIR volumes from both sets were further characterized by Kaplan Meier survival statistics, microRNA-gene correlation analyses, and GBM molecular subtype-specific distribution. Results: The top upregulated gene in both the discovery (4 fold) and validation (11 fold) sets was