title: Down-regulation of dual-specificity phosphatase 5 predicts poor prognosis of patients with prostate cancer.
abstract: Dual-specificity phosphatase 5 (DUSP5), which specifically inactivates the extracellular signal-regulated kinase (ERK) 1/2 within the mitogen-activated protein kinase (MAPK) signaling, has recently been considered to be a tumor suppressor. However, its role in prostate cancer is still elusive. In this study, we performed immunohistochemistry analysis on human tissue microarray (TMA) to detect the DUSP5 protein expression pattern. The results indicated that DUSP5 was down-regulated in the human prostate cancer relative to the adjacent benign tissues (IRS: PCa = 4.29 ± 1.72 versus Benign = 4.89 ± 1.58, P = 0.04). In addition, when we linked the DUSP5 protein levels to the clinicopathological features of the patients, we found that the downregulation of DUSP5 was significantly associated with advanced pathological stage (P = 0.004) and high Gleason score (P = 0.009). Moreover, we attempted to validate these findings and investigate the prognostic value of DUSP5 in a publicly available microarray-based Taylor Dataset. Statistic analysis demonstrated that the downregulation of DUSP5 was closely correlated with high Gleason score (P = 0.011), positive metastasis (P < 0.001) and biochemical recurrence (BCR) (P = 0.016). More importantly, Kaplan-Meier analysis revealed that significant differences between patients with high and low DUSP5 expression level in regard to the BCR-free survival of overall (P = 0.009), non-metastatic (P = 0.006) and patients with Gleason score 7 (P = 0.044). Multivariate analysis by Cox regression indicated that DUSP5 could be an independent predictor for the risk of BCR (HR: 0.41, 95% CI: 0.2-0.82; P = 0.012). In summary, our findings disclose that DUSP5 may be an important tumor suppressor that inhibits the progression of PCa. The downregulation of DUSP5 may accurately predict poor prognosis in PCa patients.
authors.affiliation: Guangdong Provincial Institute of Nephrology, Southern Medical University Guangzhou 510515, China ; Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University Guangzhou 510230, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China.
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China.
authors.forename: Zhao-Dong
authors.initials: ZD
authors.lastname: Han
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China.
authors.forename: Hui-Chan
authors.initials: HC
authors.lastname: He
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Chen
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China.
authors.forename: Sheng-Bang
authors.initials: SB
authors.lastname: Yang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China.
authors.forename: Yong-Ding
authors.initials: YD
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Institute of Nephrology, Southern Medical University Guangzhou 510515, China.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Zeng
authors.affiliation: Guangdong Provincial Institute of Nephrology, Southern Medical University Guangzhou 510515, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Liang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China.
authors.forename: Qi-Shan
authors.initials: QS
authors.lastname: Dai
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China.
authors.forename: Fu-Neng
authors.initials: FN
authors.lastname: Jiang
authors.affiliation: Guangdong Provincial Institute of Nephrology, Southern Medical University Guangzhou 510515, China ; Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University Guangzhou 510180, China ; Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University Guangzhou 510230, China.
authors.forename: Wei-De
authors.initials: WD
authors.lastname: Zhong
keywords: Prostate cancer; dual-specificity phosphatase 5; prognosis; tumor suppressor