Gene Expression Signature in Peripheral Blood Detects Thoracic Aortic Aneurysm 英文参考文献.docVIP

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Gene Expression Signature in Peripheral Blood Detects Thoracic Aortic Aneurysm 英文参考文献.doc

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Gene Expression Signature in Peripheral Blood Detects Thoracic Aortic Aneurysm 英文参考文献

GeneExpressionSignatureinPeripheralBloodDetects ThoracicAorticAneurysm YuleiWang1.,CatalinC.Barbacioru1.,DovShiffman2,SriramBalasubramanian3¤,OlgaIakoubova2,MaryannTranquilli4,GonzaloAlbornoz4, JulieBlake1,NecipN.Mehmet1,DewiNgadimo3¤,KarenPoulter1,FrancesChan1,RaymondR.Samaha1*,JohnA.Elefteriades4* 1AppliedBiosystems,FosterCity,California,UnitedStatesofAmerica,2Celera,Alameda,California,UnitedStatesofAmerica,3CeleraGenomics, South San Francisco, California, United States of America, 4Section of Cardiothoracic Surgery, Yale University School of Medicine, New Haven, Connecticut,UnitedStatesofAmerica Background. Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcomeofTAAispreventablebyelectivesurgicalrepair;however,identifyingat-riskindividualsisdifficult.Wehypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status. Our goal was to identify adistinctgeneexpressionsignatureinperipheralbloodthatmayidentifyindividualsatriskforTAA.MethodsandFindings. Whole genome gene expression profiles from 94 peripheral blood samples (collected from 58 individuals with TAA and 36 controls)wereanalyzed.SignificanceAnalysisofMicroarray(SAM)identifiedpotentialsignaturegenescharacterizingTAAvs. normal,ascendingvs.descendingTAA,andsporadicvs.familialTAA.Usingatrainingsetcontaining36TAApatientsand25 controls, a 41-gene classification model was constructed for detecting TAA status and an overall accuracy of 7866% was achieved.Testingthisclassifieronanindependentvalidationsetcontaining22TAAsamplesand11controlsyieldedanoverall classificationaccuracyof78%.These41classifiergeneswerefurthervalidatedbyTaqManHreal-timePCRassays.Classification based on the TaqManH data replicated the microarray results and achieved 80% classification accuracy on the testing set. Conclusions.ThisstudyidentifiedinformativegeneexpressionsignaturesinperipheralbloodcellsthatcancharacterizeTAA statusandsubtypesofT