The inflammation-related biomarker CXCR7 independently predicts patient outcome after radical prostatectomy

Introduction: The influence of inflammation on prostate tumor carcinogenesis is currently much better known than with its role in prostate cancer (CaP) progression. We evaluated the prognostic value of epigenetic (HDAC1, HDAC4, H3Ac) and inflammation-related (CXCR4, CXCR7, CXCL12) biomarkers immunoexpression, in radical prostatectomy specimens, from 2 cohorts of CaP patients with long term follow-up. Materials and Methods: Formalin-fixed and paraffin-embedded radical prostatectomy specimens were obtained from the pathology archives of Prof. Doutor Fernando Fonseca Hospital, in Amadora, Portugal and Portuguese Oncology Institute of Porto, in Porto, Portugal, and tissue microarrays were assembled. It was achieved a set of 234 patients submitted to radical retropubic prostatectomy between January 2000 and December 2005. Immunohistochemistry was used for evaluation of protein expression of epigenetic and inflammation-related markers. Nuclear staining was assessed using digital image analysis. Study outcomes included disease-specific survival and disease-free survival (DFS). Statistical analysis was tabulated using SPSS version 23.0. Hazard ratios (HRs) and survival curves were estimated using Cox-regression and Kaplan-Meyer models, respectively. Statistical significance was set at P < 0.05. Results: Complete follow-up data was available for 234 patients and median follow-up time was 164 [11–218] months. Patients with higher CXCR4 immunoexpression experienced significantly worse disease-specific survival compared to patients with low expression (HR = 1.016, 95% CI: 1.002–1.031). The same happened with CXCL12 (HR = 0.546 95% CI: 0.322–0.926) and H3Ac (HR = 1.015, 95% CI: 1.001c1.029). In what concerns to DFS, patients with higher expression of CXCR4 and CXCR7 were significantly more prone to experience disease recurrence (HR = 1.003, 95% CI: 1.000–1.005 and HR = 1.111, 95% CI:1.032–1.196, respectively). When adjusted to pTStage and WHO Grade Groups, CXCR7 maintained independent impact on DFS (HR = 1.119, 95% CI: 1.032–1.214). Conclusions: The interplay between inflammation and epigenetics and its impact in CaP outcome deserves further studies in the future. CXCR7 shows an independent predictor for worse DFS after radical prostatectomy, and could provide important prognostic information for patient management after radical prostatectomy.