title: Overexpression of RNF2 Is an Independent Predictor of Outcome in Patients with Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy.
abstract: RNF2 (ring finger protein 2) is frequently overexpressed in several types of human cancer, but the status of RNF2 amplification and expression in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance is unclear. In this study, immunohistochemical analysis and fluorescence in situ hybridization (FISH) were used to examine the expression and amplification of RNF2 in 184 UCB patients after radical cystectomy. Overexpression of RNF2 was observed in 44.0% of UCBs and was found to significantly associate with shortened overall and cancer-specific survival (P < 0.001). In different subsets of UCBs, RNF2 overexpression was also identified as a prognostic indicator in patients with pT1, pT2, pN(-), and/or negative surgical margins (P < 0.05). Importantly, RNF2 overexpression together with pT status and surgical margin status provided significant independent prognostic parameters in multivariate analysis (P < 0.01). FISH results showed amplification of RNF2 in 8/79 (10.1%) of informative UCB cases. Additionally, RNF2 overexpression was significantly associated with RNF2 gene amplification (P = 0.004) and cell proliferation (P = 0.003). These findings suggested that overexpression of RNF2, as examined by immunohistochemical analysis, might serve as a novel prognostic biomarker and potential therapeutic target for UCB patients who undergo radical cystectomy.
authors: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Xiang-Dong
authors: XD
authors: Li
authors: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Si-Liang
authors: SL
authors: Chen
authors: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Pei
authors: P
authors: Dong
authors: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Jie-Wei
authors: JW
authors: Chen
authors: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Feng-Wei
authors: FW
authors: Wang
authors: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Sheng-Jie
authors: SJ
authors: Guo
authors: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Li-Juan
authors: LJ
authors: Jiang
authors: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Fang-Jian
authors: FJ
authors: Zhou
authors: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Dan
authors: D
authors: Xie
authors: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.|Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Zhuo-Wei
authors: ZW
authors: Liu
mesh_terms: D049109:Cell Proliferation; D015331:Cohort Studies; D015653:Cystectomy; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery*; D019459:Urothelium / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*
chemical_list: D019394:Ki-67 Antigen; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human