K Rüenauver1, R Menon1, M A Svensson2, J Carlsson3, W Vogel1, O Andrén3, M Nowak1, S Perner1. 1. Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany. 2. 1] Department of Laboratory Medicine, University Hospital of Örebro, Örebro, Sweden [2] Department of Urology, University Hospital of Örebro, Örebro, Sweden [3] Institute of Health and Medical Science, University of Örebro, Örebro, Sweden [4] Member of the Transdisciplinary Prostate Cancer Partnership (ToPCaP). 3. 1] Department of Urology, University Hospital of Örebro, Örebro, Sweden [2] Institute of Health and Medical Science, University of Örebro, Örebro, Sweden [3] Member of the Transdisciplinary Prostate Cancer Partnership (ToPCaP).
Abstract
BACKGROUND: Prostate cancer (PCa) patients are often over-treated because of the lack of biomarkers needed to distinguish the lethal from the indolent form of PCa. YWHAZ was recently identified as a potential therapeutic target in castration-resistant PCa (CRPC). Therefore, this study focused on determining the prognostic significance of YWHAZ in localized PCa. METHODS: YWHAZ expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded tissue from 213 men who underwent radical prostatectomy. Kaplan-Meier analysis and Cox proportional-hazards models were used to assess the prognostic value of YWHAZ intensity. RESULTS: High YWHAZ expression was strongly associated with high Gleason score at the time of diagnosis (P < 0.001) and PSA relapse (P = 0.001). Importantly, patients with high expression of YWHAZ had a higher risk of CRPC development (P = 0.002) and reduced survival time (P = 0.002). CONCLUSIONS: Our findings indicate that YWHAZ could serve as a promising prognostic biomarker in localized PCa to predict poor prognosis and to identify a subgroup of tumors, which might benefit from earlier adjuvant or YWHAZ-targeted therapy.
BACKGROUND:Prostate cancer (PCa) patients are often over-treated because of the lack of biomarkers needed to distinguish the lethal from the indolent form of PCa. YWHAZ was recently identified as a potential therapeutic target in castration-resistant PCa (CRPC). Therefore, this study focused on determining the prognostic significance of YWHAZ in localized PCa. METHODS:YWHAZ expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded tissue from 213 men who underwent radical prostatectomy. Kaplan-Meier analysis and Cox proportional-hazards models were used to assess the prognostic value of YWHAZ intensity. RESULTS: High YWHAZ expression was strongly associated with high Gleason score at the time of diagnosis (P < 0.001) and PSA relapse (P = 0.001). Importantly, patients with high expression of YWHAZ had a higher risk of CRPC development (P = 0.002) and reduced survival time (P = 0.002). CONCLUSIONS: Our findings indicate that YWHAZ could serve as a promising prognostic biomarker in localized PCa to predict poor prognosis and to identify a subgroup of tumors, which might benefit from earlier adjuvant or YWHAZ-targeted therapy.
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