title: Increased nuclear factor erythroid 2-related factor 2 expression predicts worse prognosis of prostate cancer patients treated with radical prostatectomy.
abstract: Reactive 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.
authors.affiliation: Kuopio University Hospital, Department of Surgery, FI-70029 KYS, Finland; Department of Surgery, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland. Electronic address: sami.raatikainen@kuh.fi.
authors.forename: Sami
authors.initials: S
authors.lastname: Raatikainen
authors.affiliation: Kuopio University Hospital, Department of Surgery, FI-70029 KYS, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Aaltomaa
authors.affiliation: Kuopio University Hospital, Department of Clinical Pathology, FI-70029 KYS, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Kärjä
authors.affiliation: Department of Pathology and Forensic Medicine, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D060787:Neoplasm Grading; D011379:Prognosis; D011467:Prostate / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
keywords: 8-OHDG; Nrf-2; Prognosis; Prostate cancer; Radical prostatectomy