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Expression Signatures of Metastatic Capacity in a Genetic Mouse Model of Lung Adenocarcinoma 英文参考文献.docVIP

Expression Signatures of Metastatic Capacity in a Genetic Mouse Model of Lung Adenocarcinoma 英文参考文献.doc

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Expression Signatures of Metastatic Capacity in a Genetic Mouse Model of Lung Adenocarcinoma 英文参考文献

ExpressionSignaturesofMetastaticCapacityinaGenetic MouseModelofLungAdenocarcinoma DonL.Gibbons1.,WeiLin1.,ChadJ.Creighton2.*,ShulingZheng3,DrorBerel2,YananYang1 ,Maria GabrielaRaso1,4,DianeD.Liu5,IgnacioI.Wistuba1,4,GuillerminaLozano3,JonathanM.Kurie1* 1DepartmentofThoracic/HeadandNeckMedicalOncology,TheUniversityofTexas-M.D.AndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica,2DanL. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America, 3Department of Molecular Genetics, The University of Texas - M. D. AndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica,4DepartmentofPathology,TheUniversityofTexas-M.D.AndersonCancerCenter,Houston,Texas, UnitedStatesofAmerica,5BiostatisticsandAppliedMathematics,TheUniversityofTexas-M.D.AndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica Abstract Background:Non-smallcelllungcancer(NSCLC)istheforemostcauseofcancer-relateddeathinWesterncountries,which isduepartlytothepropensityofNSCLCcellstometastasize.ThebiologicbasisforNSCLCmetastasisisnotwellunderstood. Methodology/Principal Findings: Hereweaddressed thisdeficiency by transcriptionally profilingtumors fromagenetic mousemodelofhumanlungadenocarcinomathatdevelopsmetastaticdiseaseowingtotheexpressionofK-rasG12D and p53R172H.Weidentified2,209genesthatweredifferentiallyexpressedindistantmetastasesrelativetomatchedlungtumors. MiningofpubliclyavailabledatabasesrevealedthisexpressionsignatureinasubsetofNSCLCpatientswhohadapoorer prognosisthanthosewithoutthesignature. Conclusions/Significance: These findings provide evidence that K-rasG12D; p53R172H mice recapitulate features of human NSCLC metastasis and will provide a useful platform on which to study the biologic basis for lung adenocarcinoma metastasisanditspreventionbynovelagents. Citation: Gibbons DL, Lin W, Creighton CJ, Zheng S, Berel D, et al. (2009) Expression Signatures of Metastatic Capacity in a Genetic Mouse Model of Lung Adenocarcinoma.PLoSONE4(4):e5401.doi:10.1371/jo

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