Molecular Analysis of Thymoma 英文参考文献.docVIP

MolecularAnalysisofThymoma SunilBadve1,2,5*,ChirayuGoswami3,YesimGo¨kmen–Polar2,RobertP.Nelson Jr.2,JohnHenley6, NickMiller2,NarjisA.Zaheer1,GeorgeW.Sledge Jr.1,2,5,LangLi3,KennethA.Kesler4, PatrickJ.Loehrer Sr.2,5 1DepartmentofPathologyandLaboratoryMedicine,IndianaUniversitySchoolofMedicine,Indianapolis,Indiana,UnitedStatesofAmerica,2DepartmentofMedicine, IndianaUniversitySchoolofMedicine,Indianapolis,Indiana,UnitedStatesofAmerica,3CenterforComputationalBiologyandBioinformatics,IndianaUniversitySchoolof Medicine,Indianapolis,Indiana,UnitedStatesofAmerica,4DepartmentofSurgery,IndianaUniversitySchoolofMedicine,Indianapolis,Indiana,UnitedStatesofAmerica, 5Indiana University Melvin and BrenSimonCancerCenter, Indianapolis,Indiana, United States ofAmerica, 6ColumbusRegional Hospital,Columbus, Indiana, United StatesofAmerica Abstract Histologicclassificationofthymomashassignificantlimitationswithrespecttobothsubtypedefinitionsandconsistency.In ordertobetterunderstandthebiologyofthediseaseprocesses,weperformedwholegenomegeneexpressionanalysis. RNAwasextractedfromfreshfrozentumorsfrom34patientswiththymomasandfollowupdatawasavailable.Usingthe Illumina BeadStudioH platform and Human Ref-8 Beadchip, gene expression data was analyzed with Partek Genomics SuiteH,andIngenuity PathwaysAnalysis(IPA). Unsupervisedclusteringofgeneexpressiondata,representing oneofthe largest series in literature, resulted in identification of four molecular clusters of tumors (C1–C4), which correlated with histology (P=0.002). However, neither histology nor clusters correlated with clinical outcomes. Correlation of gene expressiondatawithclinicaldatashowedthatanumberofgeneswereassociatedwitheitheradvancedstageatdiagnosis ordevelopmentofrecurrenceormetastases.Thetoppathwaysassociatedwithmetastaseswereaminoacidmetabolisms, biosynthesis of steroids and glycosphingolipids, cell cycle checkpoint proteins and Notch signaling. The differential expression of some of the top genes related to b