美国FDA批准新肿瘤标志物-10-25-09

美国FDA批准新肿瘤标志物许洋中国医学科学院检验医学研发中心

PHENOMICSDISCOVERYPLATFORM

蛋白指纹图谱蛋白指纹图谱仪10年1999-2009年蛋白质组学研究与应用基因组学研究ID与定性分离纯化临床检验

PetricoinEF,ArdekaniAM,HittBA,LevinePJ,FusaroVA,SteinbergSM,MillsGB,SimoneC,FishmanDA,KohnEC,LiottaLA.FoodandDrugAdministration/NationalInstitutesofHealthClinicalProteomicsProgram,DepartmentofTherapeuticProteins/CenterforBiologicsEvaluationandResearch,FoodandDrugAdministration,Bethesda,MD,USA.petricoin@BACKGROUND:Newtechnologiesforthedetectionofearly-stageovariancancerareurgentlyneeded.Pathologicalchangeswithinanorganmightbereflectedinproteomicpatternsinserum.Wedevelopedabioinformaticstoolandusedittoidentifyproteomicpatternsinserumthatdistinguishneoplasticfromnon-neoplasticdiseasewithintheovary.METHODS:Proteomicspectraweregeneratedbymassspectroscopy(surface-enhancedlaserdesorptionandionisation).Apreliminary"training"setofspectraderivedfromanalysisofserumfrom50unaffectedwomenand50patientswithovariancancerwereanalysedbyaniterativesearchingalgorithmthatidentifiedaproteomicpatternthatcompletelydiscriminatedcancerfromnon-cancer.Thediscoveredpatternwasthenusedtoclassifyanindependentsetof116maskedserumsamples:50fromwomenwithovariancancer,and66fromunaffectedwomenorthosewithnon-malignantdisorders.FINDINGS:Thealgorithmidentifiedaclusterpatternthat,inthetrainingset,completelysegregatedcancerfromnon-cancer.Thediscriminatorypatterncorrectlyidentifiedall50ovariancancercasesinthemaskedset,includingall18stageIcases.Ofthe66casesofnon-malignantdisease,63wererecognisedasnotcancer.Thisresultyieldedasensitivityof100%(95%CI93--100),specificityof95%(87--99),andpositivepredictivevalueof94%(84--99).INTERPRETATION:Thesefindingsjustifyaprospectivepopulation-basedassessmentofproteomicpatterntechnologyasascreeningtoolforallstagesofovariancancerinhigh-riskandgeneralpopulations.Useofproteomicpatternsinserumtoidentifyovariancancer.Lancet.2002Feb16;359:572-7

CA125标准1Zhang,etal,"ThreeBiomarkersIdentifiedfromSerumProteomicAnalysisfortheDetectionofEarlyStageOvarianCancer,"CancerResearch2004;64.

标准2CA125

alone:52%

Transthyretin(转甲状腺素蛋白),ApolipoproteinA-1(载脂蛋白A1),Beta2-Microglobulin(beta2微球蛋白),Transferrin(转铁蛋白),plusCA125:94%CommonProteinsSpecificFingerprintsDiseaseProcessesPancreaticCancerOvarianCancerDiabetesTransthyretinnvhsgstffkyylqgakipkpeasfsprmnfrpgvlssrqlglpgppdvpdhaayhpfrsrqlglgppdvpdhaayhpfrDiseasespecificfingerprints

DiseasespecificfingerprintsDiseasespecifictissuereactionCirculatingproteinsOvariancancerBreastcancerPancreaticcancerBenigndiseaseClinicalTrials

ThedatademonstratesthattheOva1algorithm(Transthyretin(转甲状腺素蛋白

),ApolipoproteinA-1(载脂蛋白A1),Beta2-Microglobulin(beta2微球蛋白),Transferrin(转铁蛋白

),plusCA125)caneffectivelyidentifywomenwithahigherlikelihoodofmalignancy.Withinthestudypopulation,theOva1algorithmalsodetected90%ofStageIepithelialovariancancerca