Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin 英文参考文献.docVIP

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Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin 英文参考文献.doc

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Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin 英文参考文献

MolecularSubsetsintheGeneExpressionSignaturesof SclerodermaSkin AusraMilano1¤,SarahA.Pendergrass1,JenniferL.Sargent1,LacyK.George1,TimothyH.McCalmont5, M.KariConnolly3,4,MichaelL.Whitfield1,2 * 1DepartmentofGenetics,DartmouthMedicalSchool,Hanover,NewHampshire,UnitedStatesofAmerica,2NorrisCottonCancerCenter,DartmouthMedicalSchool, Hanover, New Hampshire, United States of America, 3Department of Dermatology, University of California San Francisco, San Francisco, California, United States of America,4DepartmentofMedicine(Rheumatology),UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica,5DepartmentofPathology, UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica Abstract Background:Sclerodermaisaclinicallyheterogeneousdiseasewithacomplexphenotype.Thediseaseischaracterizedby vasculardysfunction,tissuefibrosis,internalorgandysfunction,andimmunedysfunctionresultinginautoantibodyproduction. Methodology and Findings: We analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from distinct scleroderma subsets including 17 patients with systemic sclerosis (SSc) with diffuse scleroderma (dSSc),7patientswithSScwithlimitedscleroderma(lSSc),3patientswithmorphea,and6healthycontrols.61skinbiopsies wereanalyzedinatotalof75microarrayhybridizations.Analysisbyhierarchicalclusteringdemonstratesnearlyidentical patternsofgeneexpressionin17outof22oftheforearmandbackskinpairsofSScpatients.Usingthispropertyofthe geneexpression,weselectedasetof‘intrinsic’genesandanalyzedtheinherentdata-drivengroupings.Distinctpatternsof geneexpressionseparatepatientswithdSScfromthosewithlSScandbothareeasilydistinguishedfromnormalcontrols. OurdatashowthreedistinctpatientgroupsamongthepatientswithdSScandtwogroupsamongpatientswithlSSc.Each groupcanbedistinguishedbyuniquegeneexpressionsignaturesindicativeofproliferatingcells,immuneinfiltratesanda fibroticprogram.Theintrinsicgroupsarestatisticallysignificant(p,0.001)andeac