Radiogenomic Mapping of EdemaCellular Invasion MRI-Phenotypes in Glioblastoma Multiforme 英文参考文献.docVIP

RadiogenomicMappingofEdema/CellularInvasion MRI-PhenotypesinGlioblastomaMultiforme PascalO.Zinn1,2*,BhanuMajadan3,PratheeshSathyan1,SanjayK.Singh1,SadhanMajumder1,FerencA. Jolesz3,RivkaR.Colen3* 1DepartmentofGenetics,M.D.AndersonCancerCenter,UniversityofTexas,Houston,Texas,UnitedStatesofAmerica,2DepartmentofClinicalNeurosciences,University Hospital(CHUVBH19-110),Lausanne,Switzerland,3DepartmentofRadiology,BrighamandWomen’sHospital,HarvardMedicalSchool,Boston,Massachusetts,United StatesofAmerica Abstract Background: Despite recent discoveries of new molecular targets and pathways, the search for an effective therapy for GlioblastomaMultiforme(GBM)continues.Anewlyemergedfield,radiogenomics,linksgeneexpressionprofileswithMRI phenotypes.MRI-FLAIRisanoninvasivediagnosticmodalityandwaspreviouslyfoundtocorrelatewithcellularinvasionin GBM.Thus,ourradiogenomicscreenhasthepotentialtorevealnovelmoleculardeterminantsofinvasion.Here,wepresent the first comprehensive radiogenomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expressionprofilinginGBM. Methods:BasedonTheCancerGenomeAtlas(TCGA),discoveryandvalidationsetswithgene,microRNA,andquantitative MR-imagingdatawerecreated.TopconcordantgenesandmicroRNAscorrelatedwithhighFLAIRvolumesfrombothsets were further characterized by Kaplan Meier survival statistics, microRNA-gene correlation analyses, and GBM molecular subtype-specificdistribution. Results:Thetopupregulatedgeneinboththediscovery(4fold)andvalidation(11fold)setswasPERIOSTIN(POSTN) .The top downregulated microRNA in both sets was miR-219, which is predicted to bind to POSTN. Kaplan Meier analysis demonstrated that above median expression of POSTN resulted in significantly decreased survival and shorter time to disease progression (P,0.001). High POSTN and low miR-219 expression were significantly associated with the mesenchymalGBMsubtype(P,0.0001). Conclusion:Here,weproposeanoveldiagnosticmethodtoscreenformolecularcancersubtypesandgeno