Alteration of Gene Expression Signatures of Cortical Differentiation and Wound Response in Lethal Clear Cell Renal Cell Carcinomas 英文参考文献.docVIP
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Alteration of Gene Expression Signatures of Cortical Differentiation and Wound Response in Lethal Clear Cell Renal Cell Carcinomas 英文参考文献
AlterationofGeneExpressionSignaturesofCortical
DifferentiationandWoundResponseinLethalClearCell
RenalCellCarcinomas
HongjuanZhao1, ZongmingMa2,RobertTibshirani2,JohnP.T.Higgins3,Bo¨rjeLjungberg4,JamesD.
Brooks1*
1DepartmentofUrology,StanfordUniversity,Stanford,California,UnitedStatesofAmerica,2DepartmentofStatistics,StanfordUniversity,Stanford,California,United
States of America, 3Department of Pathology, Stanford University, Stanford, California, United States of America, 4Department of Urology, Umea? University, Umea?,
Sweden
Abstract
Clearcellrenalcellcarcinoma(ccRCC)isthemostcommonmalignancyoftheadultkidneyanddisplaysheterogeneityin
clinicaloutcomes.Throughcomprehensivegeneexpressionprofiling,wehaveidentifiedpreviouslyasetoftranscriptsthat
predict survival following nephrectomy independent of tumor stage, grade, and performance status. These transcripts,
designatedastheSPC(supervisedprincipalcomponents)geneset,shownoapparentbiologicalorgeneticfeaturesthat
provideinsightintorenalcarcinogenesisortumorprogression.Weexploredtherelationshipofthisgenelisttoasetof
genes expressed in different anatomical segments of the normal kidney including the cortex (cortex gene set) and the
glomerulus(glomerulusgeneset),andagenesetexpressedafterserumstimulationofquiescentfibroblasts(thecoreserum
responseorCSRgeneset).Interestingly,thenormalcortex,glomerulus(partofthenormalrenalcortex),andCSRgenesets
capturedmorethan1/5ofthegenesinthehighlyprognosticSPCgeneset.Basedongeneexpressionpatternsalone,the
SPCgenesetcouldbeusedtosortsamplesfromnormaladultkidneysbytheanatomicalregionsfromwhichtheywere
dissected.Tumorswhosegeneexpressionprofilesmostresembledthenormalrenalcortexorglomerulusshowedbetter
survivalthanthosethatdidnot,andthosewithexpressionfeaturesmoresimilartoCSRshowedpoorersurvival.Whilethe
cortex, glomerulus, and CSR signatures predicted survival independent of traditional clinical parameters, they were not
independentoftheSPCgenelist.Ourfindingssuggestthatcriticalbiological
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