Metabolomic Profiling from Formalin-Fixed, Paraffin-Embedded Tumor Tissue Using Targeted LCMSMS Application in Sarcoma 英文参考文献.docVIP

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Metabolomic Profiling from Formalin-Fixed, Paraffin-Embedded Tumor Tissue Using Targeted LCMSMS Application in Sarcoma 英文参考文献.doc

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Metabolomic Profiling from Formalin-Fixed, Paraffin-Embedded Tumor Tissue Using Targeted LCMSMS Application in Sarcoma 英文参考文献

MetabolomicProfilingfromFormalin-Fixed,Paraffin- EmbeddedTumorTissueUsingTargetedLC/MS/MS: ApplicationinSarcoma AndrewD.Kelly1,SusanneB.Breitkopf2,MinYuan2,JeffreyGoldsmith3,DimitriosSpentzos1,4.,JohnM. 2,4 . Asara * 1DivisionofHematology/Oncology,SarcomaProgram,BethIsraelDeaconessMedicalCenter,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica, 2Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America, 3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America, 4Department of Medicine, Harvard Medical School, Boston, Massachusetts,UnitedStatesofAmerica Abstract Therelativelynewfieldofonco-metabolomicsattemptstoidentifyrelationshipsbetweenvariouscancerphenotypesand globalmetabolitecontent.Previousmetabolomicsstudiesutilizedeithernuclearmagneticresonancespectroscopyorgas chromatography/massspectrometry,andanalyzedmetabolitespresentinurineandserum.However,directmetabolomic assessmentoftumortissuesisimportantfordeterminingalteredmetabolismincancers.Inthisrespect,theabilitytoobtain reliable data from archival specimens is desirable and has not been reported to date. In this feasibility study, we demonstrate the analysis of polar metabolites extracted directly from ten formalin-fixed, paraffin-embedded (FFPE) specimens, including five soft tissue sarcomas and five paired normal samples. Using targeted liquid chromatography- tandemmassspectrometry(LC/MS/MS)viaselectedreactionmonitoring(SRM),wedetectanaverageof106metabolites across the samples with excellent reproducibility and correlation between different sections of the same specimen. Unsupervisedhierarchicalclusteringandprincipalcomponentsanalysisreliablyrecoversaprioriknowntumorandnormal tissuephenotypes,andsupervisedanalysisidentifiescandidatemetabolicmarkerssupportedbytheliterature.Inaddition, wefindthatdiversebiochemicalprocessesarewell-representedinthelistofdete