Proteomic Analysis of Ovarian Cancer Proximal Fluids Validation of Elevated Peroxiredoxin 1 in Patient Peripheral Circulation 英文参考文献.docVIP

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Proteomic Analysis of Ovarian Cancer Proximal Fluids Validation of Elevated Peroxiredoxin 1 in Patient Peripheral Circulation 英文参考文献.doc

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Proteomic Analysis of Ovarian Cancer Proximal Fluids Validation of Elevated Peroxiredoxin 1 in Patient Peripheral Circulation 英文参考文献

ProteomicAnalysisofOvarianCancerProximalFluids: ValidationofElevatedPeroxiredoxin1inPatient PeripheralCirculation EbonyR.Hoskins1,BrianL.Hood2,MaiSun3,ThomasC.Krivak1,RobertP.Edwards1,ThomasP. Conrads2* 1DivisionofGynecologicOncology,DepartmentofObstetrics,Gynecology,andReproductiveSciencesatMagee-WomensHospitaloftheUniversityofPittsburghSchool ofMedicine,UniversityofPittsburghSchoolofMedicine,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,2GynecologicCancerCenterofExcellence,Women’sHealth IntegratedResearchCenteratInovaHealthSystem,Annandale,Virginia,UnitedStatesofAmerica,3UniversityofPittsburghCancerInstitute,Pittsburgh,Pennsylvania, UnitedStatesofAmerica Abstract Background:Epithelialovariancancer(EOC)isthedeadliestgynecologicmalignancyintheUnitedStates.Unfortunately,a validatedproteinbiomarker-screeningtesttodetectearlystagediseasefromperipheralbloodhasnotyetbeendeveloped. The present investigation assesses the ability to identify tumor relevant proteins from ovarian cancer proximal fluids, includingtissueinterstitialfluid(TIF)andcorrespondingascites,frompatientswithpapillaryserousEOCandtranslatesthese findingstotargetedblood-basedimmunoassays. Methodology/Principal Findings:PairedTIFandascitescollectedfromfourpapillaryserousEOCpatientsatthetimeof surgery underwent immunodepletion, resolution by 1D gel electrophoresis and in-gel digestion for analysis by liquid chromatography-tandemmassspectrometry,whichresultedinanaggregateidentificationof569and171proteinsfromTIF andascites,respectively.Ofthese,peroxiredoxinI(PRDX1)wasselectedforvalidationinserumbyELISAanddemonstrated tobepresentandsignificantlyelevated(p=0.0188)in20EOCpatientswithameanlevelof26.0ng/mL(69.27SEM)as comparedto4.19ng/mL(62.58SEM)from16patientswithnormal/benignovarianpathology. Conclusions/Significance: We haveutilizedaworkflow for harvesting EOC-relevantproximalbiofluids, includingTIF and ascites,forproteomicanalysis.Amongthedifferentiallyabundantproteinsidentifiedfromtheseproximalfluids,PRDX1wa