LCMS-Based Quantitative Proteomic Analysis of Paraffin-Embedded Archival Melanomas Reveals Potential Proteomic Biomarkers Associated with Metastasis 英文参考文献.docVIP

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LCMS-Based Quantitative Proteomic Analysis of Paraffin-Embedded Archival Melanomas Reveals Potential Proteomic Biomarkers Associated with Metastasis 英文参考文献.doc

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LCMS-Based Quantitative Proteomic Analysis of Paraffin-Embedded Archival Melanomas Reveals Potential Proteomic Biomarkers Associated with Metastasis 英文参考文献

LC/MS-BasedQuantitativeProteomicAnalysisof Paraffin-EmbeddedArchivalMelanomasReveals PotentialProteomicBiomarkersAssociatedwith Metastasis SharonK.Huang1,MarleneM.Darfler2,MichaelB.Nicholl1,JinsamYou3,KerryG.Bemis3,TonyJ. Tegeler3,MuWang3,Jean-PierreWery3,KellyK.Chong1,LinhdaNguyen1,RichardA.Scolyer4,DaveS.B. Hoon1* 1Department of Molecular Oncology, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, California, United States of America, 2Expression Pathology,Inc.,Gaithersburg,Maryland,UnitedStatesofAmerica,3MonarchLifeSciencesLLC,Indianapolis,Indiana,UnitedStatesofAmerica,4SydneyMelanomaUnit, SydneyCancerCenter,RoyalPrinceAlfredHospital,Camperdown,Australia Abstract Background:Melanomametastasisstatusishighlyassociatedwiththeoverallsurvivalofpatients;yet,littleisknownabout proteomicchangesduringmelanomatumorprogression.Tobetterunderstandthechangesinproteinexpressioninvolved in melanoma progression and metastasis, and to identify potential biomarkers, we conducted a global quantitative proteomicanalysisonarchivalmetastaticandprimarymelanomas. MethodologyandFindings:Atotalof16metastaticand8primarycutaneousmelanomaswereassessed.Proteinswere extractedfromlasercapturedmicrodissectedformalinfixedparaffin-embeddedarchivaltissuesbyliquefyingtissuecells. These preparations were analyzed by a LC/MS-based label-free protein quantification method. More than 1500 proteins wereidentifiedinthetissuelysateswithapeptideIDconfidencelevelof.75%.Thisapproachidentified120significant changesinproteinlevels.Theseproteinswereidentifiedfrommultiplepeptideswithhighconfidence identificationand wereexpressedatsignificantlydifferentlevelsinmetastasesascomparedwithprimarymelanomas(q-Value,0.05). ConclusionsandSignificance:Thedifferentiallyexpressedproteinswereclassifiedbybiologicalprocessormappedinto biologicalsystemnetworks,andseveralproteinswereimplicatedbytheseanalysesascancer-ormetastasis-related.These proteins represent potential biomarkers for tumor progress