p63 Expression Defines a Lethal Subset of Muscle-Invasive Bladder Cancers 英文参考文献.docVIP

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p63 Expression Defines a Lethal Subset of Muscle-Invasive Bladder Cancers 英文参考文献.doc

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p63 Expression Defines a Lethal Subset of Muscle-Invasive Bladder Cancers 英文参考文献

p63ExpressionDefinesaLethalSubsetof Muscle-InvasiveBladderCancers WoonyoungChoi1,JayB.Shah1,MaiTran2,RobertSvatek3,LaurenMarquis1,I-LingLee1,DasomYu1, LianaAdam1,SijinWen4,YuShen4,ColinDinney1,DavidJ.McConkey1,5,ArleneSiefker-Radtke6* 1DepartmentofUrology,TheUniversityofTexasM.D.AndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica,2TheGraduateSchoolofBiomedicalSciences (GSBS),UniversityofTexas-HoustonHealthSciencesCenter,Houston,Texas,UnitedStatesofAmerica,3DepartmentofUrology,TheUniversityofTexasHealthScience Center,SanAntonio,Texas,UnitedStatesofAmerica,4DepartmentofBiostatistics,TheUniversityofTexasM.D.AndersonCancerCenter,Houston,Texas,UnitedStates of America, 5Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America, 6Department of GenitourinaryMedicalOncology,TheUniversityofTexasM.D.AndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica Abstract Background: p63 is a member of the p53 family that has been implicated in maintenance of epithelial stem cell compartments. Previous studies demonstrated that p63 is downregulated in muscle-invasive bladder cancers, but the relationshipbetweenp63expressionandsurvivalisnotclear. Methodology/PrincipalFindings:Weusedreal-timePCRtocharacterizep63expressionandseveralgenesimplicatedin epithelial-to-mesenchymal transition (EMT) in human bladder cancer cell lines (n=15) and primary tumors (n=101). We correlatedtumormarkerexpressionwithstage,disease-specific(DSS),andoverallsurvival(OS).ExpressionofE-cadherinand p63 correlated directly with one another and inversely with expression of the mesenchymal markers Zeb-1, Zeb-2, and vimentin.Non-muscle-invasive(TaandT1)bladdercancersuniformlyexpressedhighlevelsofE-cadherinandp63andlow levelsofthemesenchymalmarkers.Interestingly,asubsetofmuscle-invasive(T2–T4)tumorsmaintainedhighlevelsofE- cadherinandp63expression.Asexpected,therewasastronglysignificantcorrelationbetweenEMTmarkerexpressionand muscleinvasion(p,0.