Thioredoxin Reductase Rna Levels In Expressed Prostatic Secretions Improve Prediction Of Surgical Margin Status Prior T0 Surgery

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111452 THIOREDOXIN REDUCTASE RNA LEVELS IN EXPRESSED PROSTATIC SECRETIONS IMPROVE PREDICTION OF SURGICAL MARGIN STATUS PRIOR T0 SURGERY Jennifer A. Linehan, Jarrod Clark, David Smith, Gail M. Babilonia, Kevin G. Chan, Mark H. Kawachi, Clayton S. Lau, David Y. Josephson, Tim G. Wilson, and Steven Smith Jennifer A. LinehanJennifer A. Linehan Duarte, CA More articles by this author , Jarrod ClarkJarrod Clark Duarte, CA More articles by this author , David SmithDavid Smith Duarte, CA More articles by this author , Gail M. BabiloniaGail M. Babilonia Duarte, CA More articles by this author , Kevin G. ChanKevin G. Chan Duarte, CA More articles by this author , Mark H. KawachiMark H. Kawachi Duarte, CA More articles by this author , Clayton S. LauClayton S. Lau Duarte, CA More articles by this author , David Y. JosephsonDavid Y. Josephson Duarte, CA More articles by this author , Tim G. WilsonTim G. Wilson Duarte, CA More articles by this author , and Steven SmithSteven Smith Duarte, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1365AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Suitable biomarkers in prostate cancer are needed for better clinical prognosis prior to invasive procedures. Thioredoxin reductases (TXNRD1, TXNRD2 and TGR) are involved in multiple cell functions: protection from oxidative stress, control of apoptosis, synthesis of DNA, and regulation of cell proliferation. Like TMPRSS2:ERG, the thioredoxin system has been shown to play a role in more advanced prostate cancer. We have recently used nanotechnology to demonstrate that TXNRD1 and TXNRD2 are strongly up regulated in intratumoral reactive stroma (Singer et al., In Press). Using expressed prostatic secretions (EPS) we have evaluated the utility of a new marker, TXNRD1, along with other established biomarkers to evaluate their utility as predictors of the presence of surgical margins prior to surgery in patients undergoing radical prostatectomy. METHODS We collected EPS in a blinded prospective study from 82 men undergoing radical prostatectomy for prostate cancer. Specimens were obtained just prior to radical prostatectomy. 200ng of RNA from each specimen was used to prepare cDNA for TaqMan® qPCR analysis of RNA levels. Specimens were analyzed for expression of RNA from PSA, PCA3, TXNRD1, and Type III plus VI TMPRSS2:ERG gene fusions. The capacity of these biomarkers to improve characteristic performance for predicting positive surgical margins (PSM), over baseline pre-surgical parameters: age, pre-biopsy serum PSA, biopsy Gleason sum and digital rectal exam (DRE) was analyzed. RESULTS The addition of assays for TXNRD1, PSA, PCA3, and TMPRSS2:ERG (type III+VI) RNA to baseline pre-surgical parameters for positive surgical margin prediction improved the area under the curve (AUC) from 0.728 (95%CI 0.6313728-0.8240672) to 0.862 (95%CI 0.7870411-0.9364589). At 80% specificity for positive margins, the baseline sensitivity using only DRE, PSA and biopsy Gleason sum was 56%. However, when TXNRD1, PSA, PCA3, and TMPRSS2:ERG (type III+VI), were added as predictors, the sensitivity was increased to 80% at 80% specificity. Based on these data, this test provides an 81% negative predictive value, compared to 75% for PSA, DRE and biopsy Gleason sum alone. CONCLUSIONS The combination of biopsy Gleason sum and PSA correlate strongly with positive surgical margins. The addition of TXNRD1, PSA, PCA3, and TMPRSS2:ERG(type III+VI), markers as predictors improves the sensitivity and negative predictive value in predicting positive surgical margins prior to surgery. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e582 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jennifer A. Linehan Duarte, CA More articles by this author Jarrod Clark Duarte, CA More articles by this author David Smith Duarte, CA More articles by this author Gail M. Babilonia Duarte, CA More articles by this author Kevin G. Chan Duarte, CA More articles by this author Mark H. Kawachi Duarte, CA More articles by this author Clayton S. Lau Duarte, CA More articles by this author David Y. Josephson Duarte, CA More articles by this author Tim G. Wilson Duarte, CA More articles by this author Steven Smith Duarte, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...