title: BRCC3 acts as a prognostic marker in nasopharyngeal carcinoma patients treated with radiotherapy and mediates radiation resistance in vitro.
abstract: BACKGROUND
  BRCC3 has been found to be aberrantly expressed in breast tumors and involved in DNA damage response. The contribution of BRCC3 to nasopharyngeal carcinoma prognosis and radiosensitivity is still unclear.
  
  
  METHODS
  Immunohistochemical analysis of BRCC3 was carried out in 100 nasopharyngeal carcinoma tissues, and the protein level was correlated to patient survival. BRCC3 expression of nasopharyngeal carcinoma cell lines was determined by Western-blotting and real-time PCR. Additionally, the effects of BRCC3 knockdown on nasopharyngeal carcinoma cell clongenic survival, DNA damage repair, and cell cycle distribution after irradiation was assessed.
  
  
  RESULTS
  The BRCC3 protein level was inversely correlated with nasopharyngeal carcinoma patient overall survival (P < 0.001) and 3-year loco-regional relapse-free survival (P = 0.034). Multivariate analysis demonstrated that BRCC3 expression was an independent prognostic factor (P = 0.010). The expression of BRCC3 was much higher in radioresistant nasopharyngeal carcinoma cells than in radiosensitive cells. Knockdown of BRCC3 increased the cell survival fraction, attenuated DNA damage repair and resulted in G2/M cell cycle arrest in radioresistant NPC cells.
  
  
  CONCLUSIONS
  High BRCC3 expression in nasopharyngeal carcinoma patients is associated with poor survival. BRCC3 knockdown could abate the radioresistance in nasopharyngeal carcinoma cells. These findings suggest the utility of BRCC3 as a prognostic biomarker and novel target for nasopharyngeal carcinoma.
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, No. 651, Dongfeng East Road, Guangzhou, 510060, People's Republic of China. tuzw@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. tuzw@sysucc.org.cn.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, No. 651, Dongfeng East Road, Guangzhou, 510060, People's Republic of China. 756166607@qq.com.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. 756166607@qq.com.
authors.forename: Bingqing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, No. 651, Dongfeng East Road, Guangzhou, 510060, People's Republic of China. quchen@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. quchen@sysucc.org.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Qu
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, No. 651, Dongfeng East Road, Guangzhou, 510060, People's Republic of China. taoyl@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. taoyl@sysucc.org.cn.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, No. 651, Dongfeng East Road, Guangzhou, 510060, People's Republic of China. chenchen@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. chenchen@sysucc.org.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. huawf@sysucc.org.cn.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Hua
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. fenggk@sysucc.org.cn.
authors.forename: Guokai
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, No. 651, Dongfeng East Road, Guangzhou, 510060, People's Republic of China. changhui@sysucc.org.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Chang
authors.affiliation: Department of Radiation Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China. 85172626@qq.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Affiliated Tumor Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China. 363905553@qq.com.
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China. 124915655@qq.com.
authors.forename: Changbin
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China. 897447290@qq.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. zengmsh@sysucc.org.cn.
authors.forename: Musheng
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, No. 651, Dongfeng East Road, Guangzhou, 510060, People's Republic of China. xiayf@sysucc.org.cn.|State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China. xiayf@sysucc.org.cn.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy; D004249:DNA Damage; D004260:DNA Repair; D000072017:Deubiquitinating Enzymes; D018572:Disease-Free Survival; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009303:Nasopharyngeal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy; D009363:Neoplasm Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C518017:BRCC3 protein, human; D000072017:Deubiquitinating Enzymes