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A Multi-Analyte Assay for the Non-Invasive Detection of Bladder Cancer 英文参考文献
AMulti-AnalyteAssayfortheNon-InvasiveDetectionof
BladderCancer
SteveGoodison1,4,MyronChang2,YunfengDai2,VirginiaUrquidi1,4,CharlesJ.Rosser3,4
*
1CancerResearchInstitute,M.D.AndersonCancerCenterOrlando,Orlando,Florida,UnitedStatesofAmerica,2DepartmentofBiostatistics,TheUniversityofFlorida,
Gainesville,Florida,UnitedStatesofAmerica,3SectionofUrologicOncology,MDAndersonCancerCenterOrlando,Orlando,Florida,UnitedStatesofAmerica,4Nonagen
BioscienceCorp,Orlando,Florida,UnitedStatesofAmerica
Abstract
Accurateurinaryassaysforbladdercancer(BCa)detectionwouldbenefitbothpatientsandhealthcaresystems.Through
genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can
outperformcurrenturine-basedbiomarkersforthenon-invasivedetectionofBCa.Herein,wereportthediagnosticutilityof
variousmultivariatecombinationsofthesebiomarkers.Weperformedacase-controlledvalidationstudyinwhichvoided
urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8,
MMP-9,MMP-10,SDC1,CCL18,PAI-1,CD44,VEGF,ANG,CA9,A1AT,OPN,PTX3,andAPOE)wereassessedbyenzyme-linked
immunosorbentassay(ELISA).Diagnosticperformanceofeachbiomarkerandmultivariatemodelswerecomparedusing
receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa
diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also
highlyaccurate(sensitivity90%,specificity97%).Forcomparison,thecommercialBTA-TrakELISAtestachievedasensitivity
of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These
datashowthatamultivariateurine-basedassaycanmarkedlyimprovetheaccuracyofnon-invasiveBCadetection.Further
validationstudiesareunderwaytoinvestigatetheclinicalutilityofthispanelofbiomarkersforBCadiagnosisanddisease
monitoring.
Citation: Goodison S, Chang M, Dai Y, Urquidi V, Rosser CJ (2
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