Performance of Survivin mRNA as a Biomarker for Bladder Cancer in the Prospective Study UroScreen 英文参考文献.docVIP

PerformanceofSurvivinmRNAasaBiomarkerfor BladderCancerintheProspectiveStudyUroScreen GeorgJohnen1*,KatarzynaGawrych1,HeikeBontrup1,BeatePesch1,DirkTaeger1,Se′verineBanek2, MatthiasKluckert1,3,HaraldWellha¨u?er3,FriedhelmEberle4,MichaelNasterlack4,GabrieleLeng5, ArnulfStenzl2,ThomasBru¨ning1, andtheUroScreenStudyGroup 1Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany, 2InstituteofUrology,EberhardKarlsUniversity,Tu¨bingen,Germany,3GermanSocialAccidentInsurance’sInstitutionfortheRawMaterialsandChemicalIndustry(BG RCI),Heidelberg,Germany,4OccupationalMedicineandHealthProtection,BASFSE,Ludwigshafen,Germany,5Safety-HealthProtection,CurrentaGmbHCo.OHG (formerlyBayer),Leverkusen,Germany Abstract Background:Urinarybiomarkershavethepotentialtoimprovetheearlydetectionofbladdercancer.Mostofthevarious known markers, however, have only been evaluated in studies with cross-sectional design. For proper validation a longitudinal design would be preferable. We used the prospective study UroScreen to evaluate survivin, a potential biomarkerthathasmultiplefunctionsincarcinogenesis. Methods/Results: Survivin was analyzed in 5,716 urine samples from 1,540 chemical workers previously exposed to aromaticamines.Theworkersparticipatedinasurveillanceprogramwithyearlyexaminationsbetween2003and2010.RNA wasextractedfromurinarycellsandsurvivinwasdeterminedbyReal-TimePCR.Duringthestudy,19bladdertumorswere detected. Multivariate generalized estimation equation (GEE) models showed that b-actin, representing RNA yield and quality, had the strongest influence on survivin positivity. Inflammation, hematuria and smoking did not confound the results. Survivin had a sensitivity of 21.1% for all and 36.4% for high-grade tumors. Specificity was 97.5%, the positive predictivevalue(PPV)9.5%,andthenegativepredictivevalue(NPV)99.0%. Conclusions:Inthisprospectiveandsofarlargeststudyonsurvivin,themarkershow