Expression Changes in the Stroma of Prostate Cancer Predict Subsequent Relapse 英文参考文献.docVIP

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Expression Changes in the Stroma of Prostate Cancer Predict Subsequent Relapse 英文参考文献.doc

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Expression Changes in the Stroma of Prostate Cancer Predict Subsequent Relapse 英文参考文献

ExpressionChangesintheStromaofProstateCancer PredictSubsequentRelapse ZhenyuJia1*,FarahB.Rahmatpanah1,XinChen1,WaldemarLernhardt2,YipengWang3,Xiao-QinXia4, AnneSawyers1,ManuelSutton1,MichaelMcClelland1,5*,DanMercola1* 1DepartmentofPathologyandLaboratoryMedicine,UniversityofCaliforniaIrvine,Irvine,California,UnitedStatesofAmerica,2Proveri,SanDiego,California,United StatesofAmerica,3AltheaDx,SanDiego,California,UnitedStatesofAmerica,4DepartmentofBioinformatics,InstituteofHydrobiology,ChineseAcademyofSciences, Wuhan,Hubei,China,5VaccineResearchInstituteofSanDiego,SanDiego,California,UnitedStatesofAmerica Abstract Biomarkersareneededtoaddressovertreatmentthatoccursforthemajorityofprostatecancerpatientsthatwouldnotdie of the disease but receive radical treatment. A possible barrier to biomarker discovery may be the polyclonal/multifocal nature of prostate tumors as well as cell-type heterogeneity between patient samples. Tumor-adjacent stroma (tumor microenvironment)islessaffectedbygeneticalterationandmightthereforeyieldmoreconsistentbiomarkersinresponse totumoraggressiveness.TothisendwecomparedAffymetrixgeneexpressionprofilesinstromaneartumorandidentified asetof115probesetsforwhichtheexpressionlevelsweresignificantlycorrelatedwithtime-to-relapse.Wealsocompared patientsthatchemicallyrelapsedshortlyafterprostatectomy(,1year),andpatientsthatdidnotrelapseinthefirstfour yearsafterprostatectomy.Weidentified131differentiallyexpressedmicroarrayprobesetsbetweenthesetwocategories. 19probesets(15genesoverlappedbetweenthetwogenelistswithp,0.0001).WedevelopedaPAM-basedclassifierby trainingonsamplescontainingstromaneartumor:9rapidrelapsepatientsamplesand9indolentpatientsamples.Wethen tested the classifier on 47 different samples, containing 90% or more stroma. The classifier predicted the risk status of patients with an average accuracy of 87%. This is the first general tumor microenvironment-based prognostic classifier. These results indicate that the prostate cancer microenvironm