Molecular Sub-Classification of Renal Epithelial Tumors Using Meta-Analysis of Gene Expression Microarrays 英文参考文献.docVIP

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Molecular Sub-Classification of Renal Epithelial Tumors Using Meta-Analysis of Gene Expression Microarrays 英文参考文献.doc

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Molecular Sub-Classification of Renal Epithelial Tumors Using Meta-Analysis of Gene Expression Microarrays 英文参考文献

MolecularSub-ClassificationofRenalEpithelialTumors UsingMeta-AnalysisofGeneExpressionMicroarrays ThomasSanford1,PaulH.Chung1,ArielReinish1,VladimirValera1,RamaprasadSrinivasan1,W.Marston Linehan1,GennadyBratslavsky1,2* 1Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland, United States of America, 2Department of Urology, Upstate Medical University, State UniversityofNewYork,Syracuse,NewYork,UnitedStatesofAmerica Abstract Purpose:Toevaluatetheaccuracyofthesub-classificationofrenalcorticalneoplasmsusingmolecularsignatures. ExperimentalDesign:Asearchofpubliclyavailabledatabaseswasperformedtoidentifymicroarraydatasetswithmultiple histologicsub-typesofrenalcorticalneoplasms.Meta-analytictechniqueswereutilizedtoidentifydifferentiallyexpressed genes for each histologic subtype. The lists of genes obtained from the meta-analysis were used to create predictive signaturesthroughtheuseofapair-basedmethod.Thesesignatureswereorganizedintoanalgorithmtosub-classifyrenal neoplasms.Theuseofthesesignaturesaccordingtoouralgorithmwasvalidatedonseveralindependentdatasets. Results: We identified three Gene Expression Omnibus datasets that fit our criteria to develop a training set. All of the datasetsinourstudyutilizedtheAffymetrixplatform.Thefinaltrainingdatasetincluded149samplesrepresentedbythe four most common histologic subtypes of renal cortical neoplasms: 69 clear cell, 41 papillary, 16 chromophobe, and 23 oncocytomas.Whenvalidationofoursignatureswasperformedonexternaldatasets,wewereabletocorrectlyclassify68of the72samples(94%).Thecorrectclassificationbysubtypewas19/20(95%)forclearcell,14/14(100%)forpapillary,17/19 (89%)forchromophobe,18/19(95%)foroncocytomas. Conclusions:Throughtheuseofmeta-analytictechniques,wewereabletocreateanalgorithmthatsub-classifiedrenal neoplasms on a molecular level with 94% accuracy across multiple independent datasets. This algorithm may aid in selectingmoleculartherapiesandmayimprovetheaccuracyofsubtypingofrenalcorticaltumors. Cit