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Gene Expression Signatures That Predict Radiation Exposure in Mice and Humans 英文参考文献
o
PL SMEDICINE
GeneExpressionSignaturesThatPredict
RadiationExposureinMiceandHumans
Holly K.Dressman1,2,Garrett G.Muramoto3,Nelson J.Chao3,Sarah Meadows3,Dawn Marshall3,Geoffrey S.Ginsburg1,
Joseph R.Nevins1,2,John P.Chute1,3*
1InstituteforGenomeSciencesandPolicy,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica,2DepartmentofMolecularGeneticsand
Microbiology,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica,3DivisionofCellularTherapy,DepartmentofMedicine,DukeUniversity
MedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica
Funding:Thisresearchwas
supported,inpart,bygrantAI-
067798–01fromtheNational
InstitutesofAllergyandInfectious
Diseases(JRNandJPC).Thefunders
hadnoroleinstudydesign,data
collectionandanalysis,decisionto
publish,orpreparationofthe
manuscript.
ABSTRACT
Background
Thecapacitytoassessenvironmentalinputstobiologicalphenotypesislimitedbymethods
thatcanaccuratelyandquantitativelymeasurethesecontributions.Onesuchexamplecanbe
seeninthecontextofexposuretoionizingradiation.
CompetingInterests:Theauthors
havedeclaredthatnocompeting
interestsexist.
MethodsandFindings
Wehavemadeuseofgeneexpressionanalysisofperipheralblood(PB)mononuclearcellsto
develop expression profiles that accurately reflect prior radiation exposure. We demonstrate
thatexpressionprofilescanbedevelopedthatnotonlypredictradiationexposureinmicebut
alsodistinguishthelevelofradiationexposure,rangingfrom50cGyto1,000cGy.Likewise,a
molecular signature of radiation response developed solely from irradiated human patient
samplescanpredictanddistinguishirradiatedhumanPBsamplesfromnonirradiatedsamples
withanaccuracyof90%,sensitivityof85%,andspecificityof94%.Wefurtherdemonstratethat
aradiationprofiledevelopedinthemousecancorrectlydistinguishPBsamplesfromirradiated
andnonirradiatedhumanpatientswithanaccuracyof77%,sensitivityof82%,andspecificityof
75%.Takentogether,thesedatademonstratethatmolecularprofilescanbegeneratedthatare
highlypredictiveofdifferentlevels
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