临床免疫学—讨论课1-文献阅读与评价.ppt

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1、EvaluationofUrineAquaporin1andPerilipin2ConcentrationsasBiomarkerstoScreenforRenalCellCarcinoma文献阅读与评价Importanceofresearch1.Earlydetectionofsmallasymptomatickidneytumorspresagesbetterpatientoutcome.2.Incidentaldiscoveryofasymptomaticrenaltumorsbyabdominalimagingisexpens

2、iveandcannotreliablydistinguishbenignfrommalignanttumors.PurposeofresearchToevaluatetheclinicalutility,sensitivityandspecificityofurineaquaporin-1(AQP1)andperilipin-2(PLIN2)concentrationsasuniquenoninvasivebiomarkerstodiagnosemalignantclearcellorpapillaryrenalcellcarcin

3、oma(RCC)inascreeningparadigm.WhytofocusonAQP1andPLIN2OurpreviousstudieshaveshownthatAQP1andPLIN2concentrationsweresignificantlyhigherinpatientswithclearcellandpapillarycancerscomparedwithcontrols,werecorrelatedwithtumorsize,andstage(butnotgrade),andweredecreasedover83%f

4、ollowingtumorexcision.UrineconcentrationsofAQP1orPLIN2werenotincreasedinpatientswitha)commonnon-cancerouskidneydiseasessuchasdiabeticnephropathy,glomerulonephritisandurinarytractinfections,b)non-cancerouskidneytumors(oncocytomas,angiomyolipomas),orc)bladderorprostatecan

5、cer.Thesestudiesareconsistentwiththefirsttwophasesofdiagnosticcancerbiomarkerdevelopmentbyidentifyingpromisingbiomarkers(phase1)andestablishingthatthebiomarkersidentifyclinicaldiseasefrompotentialconfoundingdiseases(phase2).HowtodoUrinesampleswereobtainedfrom720patients

6、undergoingroutineabdominalCT(screeningpopulation,including334nohistoryofcancerand386withhistoryofcancer),80healthycontrolsand19patientswithpathologicallyconfirmedRCC.UrineAQP1andPLIN2concentrationsweremeasuredbysensitiveandspecificELISAandWesternblotprocedures,respectiv

7、ely.ClinicalandpathologicaldataResultsFigure1.DotandboxrepresentationofurineAQP1(A)andPLIN2(B)concentrations.Depictedarethemedian,first,second,thirdandfourthquartiles.Figure2.Correlationbetweentumorsizeandurinebiomarkersinthe19patientsenrolledaprioriwithkidneycancer(cle

8、arcellorpapillarysubtypes).(A)AQP1concentrations(Spearmancorrelationcoefficient0.78,P<0.001)or(B)PLIN2concentr