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The Prognostic PDE4D7 Score in a Diagnostic Biopsy Prostate Cancer Patient Cohort with Longitudinal Biological Outcomes

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Dianne Van Strijp, Christiane De Witz, Pieter C. Vos, Eveline Den Biezen-Timmermans, Anne Van Brussel, Janneke Wrobel, George S. Baillie, Pierre Tennstedt, Thorsten Schlomm, Birthe Heitkötter, Sebastian Huss, Martin Bögemann, Miles D. Houslay, Chris Bangma, Axel Semjonow, Ralf Hoffmann

Original languageEnglish
Article number5821616
JournalProstate Cancer
Volume2018
DOIs
Accepted/In press11 Jul 2018
Published26 Jul 2018

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Abstract

Purpose. To further validate the prognostic power of the biomarker PDE4D7, we investigated the correlation of PDE4D7 scores adjusted for presurgical clinical variables with longitudinal postsurgical biological outcomes. Methods. RNA was extracted from biopsy punches of resected tumors (550 patients; RP cohort) and diagnostic needle biopsies (168 patients; DB cohort). Cox regression and survival were applied to correlate PDE4D7 scores with patient outcomes. Logistic regression was used to combine the clinical CAPRA score with PDE4D7. Results. In univariate analysis, the PDE4D7 score was significantly associated with PSA recurrence after prostatectomy in both studied patient cohorts' analysis (HR 0.53; 95% CI 0.41-0.67; p<1.0E-04 and HR 0.47; 95% CI 0.33-0.65; p<1.0E-04, respectively). After adjustment for the presurgical clinical variables preoperative PSA, PSA density, biopsy Gleason, clinical stage, percentage tumor in the biopsy (data only available for RP cohort), and percentage of positive biopsies, the HR was 0.49 (95% CI 0.38-0.64; p<1.0E-04) and 0.43 (95% CI 0.29-0.63; p<1.0E-04), respectively. The addition of the PDE4D7 to the clinical CAPRA score increased the AUC by 5% over the CAPRA score alone (0.82 versus 0.77; p=0.004). This combination model stratified 14.6% patients of the DB cohort to no risk of biochemical relapse (NPV 100%) over a follow-up period of up to 15 years. Conclusions. The PDE4D7 score provides independent risk information for pretreatment risk stratification. Combining CAPRA with PDE4D7 scores significantly improved the clinical risk stratification before surgery.

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