Increased nuclear factor erythroid 2–related factor 2 expression predicts worse prognosis of prostate cancer patients treated with radical prostatectomy

SummaryReactive oxygen species are known to be linked with cell damage leading to carcinogenesis. Augmented levels of oxidative stress biomarkers, such as nuclear factor erythroid 2–related factor 2 (Nrf-2) and 8-hydroxydeoxyguanosine (8-OHDG), have been shown to associate with more aggressive behavior in many malignancies. The aim of this study was to determine whether Nrf-2 and 8-OHDG expression could predict the outcome in radical prostatectomy patients. Samples of 240 prostate cancer patients were analyzed for Nrf-2 and 8-OHDG expression by immunohistochemistry. The results were compared with clinicopathological data, biochemical recurrence–free survival (BFS), prostate cancer–specific survival, and overall survival (OS). Positive expression of 8-OHDG (P < .0001), Nrf-2 in cytoplasm (c-Nrf-2) (P = .015), and Nrf-2 in nucleus (n-Nrf-2) (P = .016) was more abundant in malignant tissue compared with benign, respectively. Elevated level of c-Nrf-2 expression was associated with positive surgical marginal (P = .005), extraprostatic extension (P = .031), biochemical recurrence (BCR) (P = .030), and OS (P = .002); and n-Nrf-2 expression was associated with pathologic stage class (P = .001), Gleason score (P = .026), extraprostatic extension (P = .027), BCR (P = .037), and OS (P < .0001). The increased c-Nrf-2 expression predicted shortened BFS (P = .034) and worse OS (P = .017). In the multivariate analysis, c-Nrf-2 (P = .028 and P = .019) and Gleason score (P = .001 and P = .033) were independent predictors of BFS and OS, respectively. Expression of the analyzed biomarkers was not linked with prostate cancer–specific survival. Expression of 8-OHDG was not associated with any clinicopathological factors or survival. These results reveal that increased c-Nrf-2 expression is a predictor of BFS and OS in conjunction with Gleason score in prostate cancer patients treated with radical prostatectomy.