An Attempt at a Molecular Prediction of Metastasis in Patients with Primary Cutaneous Melanoma 英文参考文献.docVIP

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An Attempt at a Molecular Prediction of Metastasis in Patients with Primary Cutaneous Melanoma 英文参考文献.doc

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An Attempt at a Molecular Prediction of Metastasis in Patients with Primary Cutaneous Melanoma 英文参考文献

AnAttemptataMolecularPredictionofMetastasisin PatientswithPrimaryCutaneousMelanoma MelanieGschaider1,FriederikeNeumann2,BettinaPeters3,FlorianLenz2,MichaelCibena2, MalgorzataGoiser1,IngridWolf4,Jo¨rgWenzel5,CorneliaMauch6,WolfgangSchreiner2, StephanN.Wagner1* 1DivisionofImmunology,AllergyandInfectiousDiseases,DepartmentofDermatology,MedicalUniversityofVienna,Vienna,Austria, 2SectionforBiosimulationand Bioinformatics,CenterforMedicalStatistics,InformaticsandIntelligentSystems,MedicalUniversityofVienna,Vienna,Austria,3ProjectManagementAgency,Memberof German Aerospace Centre, Health Research, Bonn, Germany, 4Department of Dermatology, Medical University of Graz, Graz, Austria, 5Department of Dermatology, UniversityofBonn,Bonn,Germany,6DepartmentofDermatology,UniversityofCologne,Cologne,Germany Abstract Background:Currentprognosticclinicalandmorphologicalparametersareinsufficienttoaccuratelypredictmetastasisin individualmelanomapatients.Severalstudieshavedescribedgeneexpressionsignaturestopredictsurvivalormetastasisof primarymelanomapatients,howeverthereproducibilityamongthesestudiesisdisappointinglylow. Methodology/PrincipalFindings:WefollowedextendedREMARK/GouldRothbergcriteriatoidentifygenesetspredictive formetastasisinpatientswithprimarycutaneousmelanoma.Forclasscomparison,geneexpressiondatafrom116patients withclinicalstageI/II(nometastasis)and72withIII/IVprimarymelanoma(withmetastasis)attimeoffirstdiagnosiswere used.Significanceanalysisofmicroarraysidentifiedthetop50differentiallyexpressedgenes.Inanindependentdataset fromasecondcohortof28primarymelanomapatients,thesegeneswereanalyzedbymultivariateCoxregressionanalysis andleave-one-outcrossvalidationforassociationwithdevelopmentofmetastaticdisease.InamultivariateCoxregression analysis, expression of the genes Ena/vasodilator-stimulated phosphoprotein-like (EVL) and CD24 antigen gave the best predictivevalue(p=0.001;p=0.017,respectively).AmultivariateCoxproportionalhazardsmodelrevealedthesegenesasa potenti