Global MicroRNA Expression Profiling of High-Risk ER+ Breast Cancers from Patients Receiving Adjuvant Tamoxifen Mono-Therapy A DBCG Study 英文参考文献.docVIP

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Global MicroRNA Expression Profiling of High-Risk ER+ Breast Cancers from Patients Receiving Adjuvant Tamoxifen Mono-Therapy A DBCG Study 英文参考文献.doc

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GlobalMicroRNAExpressionProfilingofHigh-RiskERBreastCancersfromPatientsReceivingAdjuvantTamoxifenMono-TherapyADBCGStudy英文参考文献

GlobalMicroRNAExpressionProfilingofHigh-RiskER+ BreastCancersfromPatientsReceivingAdjuvant TamoxifenMono-Therapy:ADBCGStudy MariaB.Lyng1*,Anne-VibekeL?nkholm2,RolfS?kilde3,KarinaH.Gravgaard1,ThomasLitman3, HenrikJ.Ditzel1,4 * 1InstituteofMolecularMedicine,UniversityofSouthernDenmark,Odense,Denmark,2DepartmentofPathology,SlagelseHospital,Slagelse,Denmark,3Departmentof BiomarkerDiscovery,ExiqonA/S,Vedb?k,Denmark,4DepartmentofOncology,OdenseUniversityHospital,Odense,Denmark Abstract Purpose: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors developresistance.MicroRNAs(miRNAs)havebeensuggestedaspromisingbiomarkersandwehereevaluatedwhethera miRNAprofilecouldbeidentified,sub-groupingER+breastcancerpatientstreatedwithadjuvantTamoxifenwithregardsto probabilityofrecurrence. Experimental Design: Global miRNA analysis was performed on 152ER+ primary tumors from high-risk breast cancer patientswithaninitialdiscoverysetof52patients,followedbytwoindependenttestsets(N=60andN=40).Allpatients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half haddeveloped distant recurrence(mediantime-to-recurrence:3.5years).MiRNAexpressionwasexaminedbyunsupervisedhierarchicalclustering andsupervisedanalysis,includingclinicalparametersasco-variables. Results:Thediscoverysetidentified10highlysignificantmiRNAsthatdiscriminatedbetweenthepatientsamplesaccording tooutcome.However,thesubsequenttwoindependenttestsetsdidnotconfirmthepredictivepotentialofthesemiRNAs. AsignificantcorrelationwasidentifiedbetweenmiR-7andthetumorgrade.InvestigationofthemicroRNAswiththemost variableexpressionbetweenpatientsindifferentrunsyieldedalistof31microRNAs,eightofwhichareassociatedwith stemcellcharacteristics. Conclusions:Basedonthelargesamplesize,ourdatastronglysuggeststhatthereisnosinglemiRNAprofilepredictiveof outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified