title: COP1, the negative regulator of ETV1, influences prognosis in triple-negative breast cancer.
abstract: BACKGROUND
  ETS variant 1 (ETV1) and E3 ubiquitin ligase constitutive photomorphogenetic 1 (COP1) have been proposed to be a pair of oncogene and tumor suppressor. However, the co-existing status of ETV1 and COP1 in triple-negative breast cancer (TNBC) and their predictive role in determining the patient's outcome are uncertain.
  
  
  METHODS
  We examined the abundance of COP1 and ETV1 proteins and their clinicopathologic significance in archival TNBC tissues from 105 patients by tissue microarray. The potential function link between COP1 and ETV1 was observed in MDA-MB-231 cells by cell proliferation, invasion and migration assays.
  
  
  RESULTS
  ETV1 expression was higher in TNBC tissues compared to normal tissues, while COP1 was lower. ETV1 expression was negatively associated with COP1 abundance in TNBCs. Overexpression of COP1 led to significant reduction of ETV1 in MDA-MB-231 cells, and suppressed the cells migration and invasion. Rescue of ETV1 expression in the presence of COP1 notably regained the cells behaviors. ETV1-positive group was associated with a markedly poor overall survival. Meanwhile, we had observed favourable prognosis in COP1-positive cases for the first time. Multivariate analysis showed that COP1 together with ETV1 were independent risk factors in the prognosis of TNBC patients.
  
  
  CONCLUSIONS
  COP1 might be a tumor suppressor by negative regulating ETV1 in patients with TNBCs. COP1 and ETV1 are a pair of independent predictors of prognosis for TNBC cases. Thus, targeting them might be a potential strategy for personalized TNBC treatment.
authors.affiliation: Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. wyb714@aliyun.com.|Department of Clinical Laboratory, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. wyb714@aliyun.com.
authors.forename: Mao
authors.initials: M
authors.lastname: Ouyang
authors.affiliation: Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. wh_hua225@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. nurch@126.com.
authors.forename: Jieyi
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Vascular, Thyroid and Breast Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. 21746238@qq.com.
authors.forename: Weiming
authors.initials: W
authors.lastname: Lü
authors.affiliation: Department of Vascular, Thyroid and Breast Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. lijie3218@sina.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Vascular, Thyroid and Breast Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. yaochen_sums@163.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Vascular, Thyroid and Breast Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. 13922231628@163.com.
authors.forename: Guangqi
authors.initials: G
authors.lastname: Chang
authors.affiliation: Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. bijiong2000@hotmail.com.
authors.forename: Jiong
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Vascular, Thyroid and Breast Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. shenminggz@126.com.
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Rd II, Guangzhou, Guangdong, 510080, People's Republic of China. w166w2000@aliyun.com.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate / Q000639:trends; D014157:Transcription Factors / Q000096:biosynthesis*; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; D014157:Transcription Factors; C471981:COP1 protein, human; D044767:Ubiquitin-Protein Ligases