Review
©2011byTheAmericanSocietyforBiochemistryandMolecularBiology,Inc.Thispaperisavailableonlineathttp://doc.docsou.com
MassSpectrometryBasedGlycoproteomics—FromaProteomicsPerspective*
ShengPan ,RuChen§,RuediAebersold¶,andTeresaA.Brentnall§
Glycosylationisoneofthemostimportantandcommonformsofproteinpost-translationalmodificationthatisinvolvedinmanyphysiologicalfunctionsandbiologicalpathways.Alteredglycosylationhasbeenassociatedwithavarietyofdiseases,includingcancer,inflammatoryanddegenerativediseases.Glycoproteinsarebecomingim-portanttargetsforthedevelopmentofbiomarkersfordiseasediagnosis,prognosis,andtherapeuticresponsetodrugs.Theemergingtechnologyofglycoproteomics,whichfocusesonglycoproteomeanalysis,isincreasinglybecominganimportanttoolforbiomarkerdiscovery.Anin-depth,comprehensiveidentificationofaberrantglyco-proteins,andfurther,quantitativedetectionofspecificglycosylationabnormalitiesinacomplexenvironmentre-quireaconcertedapproachdrawingfromavarietyoftechniques.Thisreportprovidesanoverviewoftherecentadvancesinmassspectrometrybasedglycoproteomicmethodsandtechnology,inthecontextofbiomarkerdis-coveryandclinicalapplication.Molecular&CellularProteomics10:10.1074/mcp.R110.003251,1–14,2011.
tocancer(4–6).Recentreportshaveprovidedacomprehen-siveoverviewoftheconceptofglycomicsanditsprospectiveinbiomarkerresearch(7–10).Incontrast,thisreviewisfo-cusedonrecentdevelopmentsinglycoproteomictechniquesandtheiruniqueapplicationandtechnicalchallengetobio-markerdiscovery.
GlycoproteomicsinBiomarkerDiscoveryandClinicalStudy—Mostsecretoryandmembrane-boundproteinspro-ducedbymammaliancellscontaincovalentlylinkedglycanswithdiversestructures(2).Theglycosylationformofaglyco-proteinishighlyspecificateachglycosylationsiteandgen-erallystableforagivencelltypeandphysiologicalstate.However,theglycosylationformofaproteincanbealteredsignificantlybecauseofchangesincellularpathwaysandprocessesresultingfromdiseases,suchascancer,inflamma-tion,andneurodegeneration.Suchdisease-associatedalter-ationsinglycoproteinscanhappeninoneorbothoftwoways:1)proteinglycosylationsitesareeitherhypo,hyper,ornewlyglycosylatedand/or;2)theglycosylationformoftheattachedcarbohydratemoietyisaltered.Infact,alteredgly-cosylationpatternshavelongbeenrecognizedashallmarksincancerprogression,inwhichtumor-specificglycoproteinsareactivelyinvolvedinneoplasticprogressionandmetastasis(5,6,11,12).Sensitivedetectionofsuchdisease-associatedglycosylationchangesandabnormalitiescanprovideauniqueavenuetodevelopglycoproteinbiomarkersfordiag-nosisandprognosis.Inaddition,interventionintheglycosyl-ationandcarbohydrate-dependentcellularpathwaysrepre-sentapotentialnewmodalityforcancertherapies(6,11,13).TableIlistssomeoftheFDAapprovedcancerbiomarkers(14,15)thatareglycosylatedproteinsorproteincomplexes.
Proteinbiomarkerdevelopmentisacomplexandchalleng-ingtask.Thecriteriaandapproachappliedfordevelopingeachindividualbiomarkercanvary,dependingonthepur-poseofthebiomarkerandtheperformancerequirementforitsclinicalapplication(16,17).Ingeneral,ithasbeensug-gestedthatthepreclinicalexploratoryphaseofproteinbio-markerdevelopmentcanbetechnicallydefinedintofourstages(18),includinginitialdiscoveryofdifferentialproteins;testingandselectionofqualifiedcandidates;verificationofasubsetofcandidates;assaydevelopmentandpre-clinicalvalidationofpotentialbiomarkers.Thankstorecenttechno-logicaladvances,massspectrometrybasedglycoproteomicsisnowplayingamajorroleintheinitialphaseofdiscovering
Withrecentadvancesinproteomics,analyticalandcom-putationaltechnologies,glycoproteomics—theglobalanaly-sisofglycoproteins—israpidlyemergingasasubfieldofproteomicswithhighbiologicalandclinicalrelevance.Glyco-proteomicsintegratesglycoproteinenrichmentandproteo-micstechnologiestosupportthesystematicidentificationandquantificationofglycoproteinsinacomplexsample.There-centdevelopmentofthesetechniqueshasstimulatedgreatinterestinapplyingthetechnologyinclinicaltranslationalstudies,inparticular,proteinbiomarkerresearch.
Whileglycomicsisthestudyofglycome(repertoireofgly-cans),glycoproteomicsfocusesonstudyingtheprofileofglycosylatedproteins,i.e.theglycoproteome,inabiologicalsystem.Considerableworkhasbeendonetocharacterizethesequencesandprimarystructureoftheglycanmoietiesat-tachedtoproteins(1–3),andtheirstructuralalterationsrelated
Fromthe DepartmentofPathology,UniversityofWashington,Seattle,WA98195,§DivisionofGastroenterology/DepartmentofMedicine,UniversityofWashington,Seattle,WA98195,¶InstituteofMolecularSystemsBiology,ETHZurichandFacultyofScience,UniversityofZurich,Switzerland
ReceivedAugust27,2010,andinrevisedform,September2,2010Published,MCPPapersinPress,August27,2010,DOI10.1074/mcp.R110.003251
Molecular&CellularProteomics10.110.1074/mcp.R110.003251–1
Glycomicsand glycoproteomics 4. Top-down proteomics ...Mass Spectrometry-based Molecular Imaging and ...Proteomics (CNCP-2014) Informatics from a ...
proteomics level involving structural information of ...glycoproteomics-based discovery research into new ...mass spectrometry (MS) to determine both the ...
from the omics (e.g. genomics and proteomics) ...HPLC systems coupled with mass spectrometry). Sub...glycoproteomics and other methods to detect chemically...
proteomics level involving structural information of ...glycoproteomics-based discovery research into new ...mass spectrometry (MS) to determine both the ...
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