The prognostic value of ribonucleotide reductase small subunit M2 in predicting recurrence for prostate cancers

Purpose: To investigate the prognostic e of bonucle 'd eductase small subunit M2 (RRM2) in low- and intermediate-risk prostate cancer (PCa). Materials and methods: A retrospective outcome study was conducted on 164 eligible PCa samples from the City of hope (n = 90) and the Taipei Medical University (n = 74). The RRM2 protein levels were detected by immunohistochemistry. Biochemical recurrence was assessed using Kaplan-Meier and Cox proportional hazard analyses. Cell invasion assays. Ras/Ral, and matrix metallopeptidase 9 activities were determined to evaluate the role of RRM2 on invasiveness of PCa. Results: Expression of RRM2 was significantly increased in patients with higher Gleason score, who had advanced T stage, and who were margin/capsule positive (P < 0.05). Analysis revealed that the expression of RRM2 positively associated with biochemical recurrence of PCa in the City of Hope set (hazard ratio = 5.26; 95% CI 1.50-24.71) and the Taipei Medical University set (hazard ratio = 2.55; 95% ('1 1.30-9.22). In stratification analysis. RRM2 was significantly correlated with poor outcome in patients with lower-risk PCa, including those with Gleason score 4 to 7, margin(-), capsule(-), and stage T1-T2. In patients with Gleason score 4 to 7, the risk of recurrence was pmportional to R1012 protein levels. The prognostic performance of RRM2 was superior to that of pathoclinical factors, including margin/ capsule status and T stage. An in vitro study demonstrated that RRM2 could promote tumor invasion activities in PCa cell lines. Suppression of RRM2 reduced the Ras/Raf and matrix metallopeptidase 9 activities. Conclusion: RRM2 plays a critical role in proliferation and invasion of PCa. Adding RRM2 as a biomarker in clinical assessments may increase model precision in predicting recurrence in patients.vith low -risk PC.a. (C) 2014 Elsevier Inc:. All rights reserved.