Validation of cyclic adenosine monophosphate phosphodiesterase-4D7 for its independent contribution to risk stratification in a prostate cancer patient cohort with longitudinal biological outcomes

de Inda, M. A. et al. (2018) Validation of cyclic adenosine monophosphate phosphodiesterase-4D7 for its independent contribution to risk stratification in a prostate cancer patient cohort with longitudinal biological outcomes. European Urology Focus, 4(3), pp. 376-384. (doi: 10.1016/j.euf.2017.05.010) (PMID:28753810)

Abstract

Background: The clinical metrics used to date to assess the progression risk of newly diagnosed prostate cancer patients only partly represent the true biological aggressiveness of the underlying disease. Objective: Validation of the prognostic biomarker phosphodiesterase-4D7 (PDE4D7) in predicting longitudinal biological outcomes in a historical surgery cohort to improve postsurgical risk stratification. Design, patients, and methods: RNA was extracted from biopsy punches of resected tumors from 550 patients. PDE4D7 was quantified using one-step quantitative reverse transcription-polymerase chain reaction. PDE4D7 scores were calculated by normalization of PDE4D7 to reference genes. Multivariate analyses were adjusted for clinical prognostic variables. Outcomes tested were: prostate-specific antigen relapse, start of salvage treatment, progression to metastases, overall mortality, and prostate cancer-specific mortality. The PDE4D7 score was combined with the clinical risk model Cancer of the Prostate Risk Assessment Postsurgical Score (CAPRA-S) using multivariate regression modeling; the combined score was tested in post-treatment progression free survival prediction. Outcome measurements and statistical analysis: Correlations with outcomes were analyzed using multivariate Cox regression and logistic regression statistics. Results and limitations: The PDE4D7 score was significantly associated with time-to-prostate specific antigen failure after prostatectomy (hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.41–0.67 for each unit increase, p < 0.0001). After adjustment for postsurgical prognostic variables the HR was 0.56 (95% CI: 0.43–0.73, p < 0.0001). The PDE4D7 score remained significant after adjusting the multi-variate analysis for the CAPRA-S model categories (HR = 0.54, 95% CI = 0.42–0.69, p < 0.0001). Combination of the PDE4D7 score with the CAPRA-S demonstrated a significant incremental value of 4–6% in 2-yr (p = 0.004) or 5-yr (p = 0.003) prediction of progression free survival after surgery. The combined model of PDE4D7 and CAPRA-S improves patient selection with very high risk of fast disease relapse after primary intervention. Conclusions: The PDE4D7 score has the potential to provide independent risk information and to restratify patients with clinical intermediate- to high-risk characteristics to a very low-risk profile.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Houslay, Professor Miles and Baillie, Professor George
• Authors: de Inda, M. A., van Strijp, D., den Biezen-Timmermans, E., van Brussel, A., Wrobel, J., van Zon, H., Vos, P., Baillie, G. S., Tennstedt, P., Schlomm, T., Houslay, M. D., Bangma, C., and Hoffmann, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: European Urology Focus
• Publisher: Elsevier
• ISSN: 2405-4569
• ISSN (Online): 2405-4569
• Published Online: 13 June 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in European Urology Focus 4(3): 376-384
• Publisher Policy: Reproduced under a Creative Commons License