title: Overexpression of ETV4 protein in triple-negative breast cancer is associated with a higher risk of distant metastasis.
abstract: BACKGROUND
  Patients with triple-negative breast cancer (TNBC) present a higher probability of distant metastasis and lack of effective targeted therapy. ETS translocation variant 4 (ETV4) is an ETS (E-26) transcription factor and has been associated with tumor metastasis. However, the clinical and functional significance of ETV4 in TNBC still remains unclear.
  
  
  METHODS
  A human tumor metastasis polymerase chain reaction array was used to profile differential expression of tumor metastasis-related genes in TNBC tissue. Real-time reverse transcription and Western blot analyses were performed to verify ETV4 expression in TNBC cells and tissue. Immunohistochemistry was used to detect expression of ETV4 protein in 135 TNBC tissue samples for association between ETV4 protein expression and clinical outcomes.
  
  
  RESULTS
  A total total of eight upregulated (CCL7, KISS1, MET, MMP7, NR4A3, ETV4, TIMP3, and TSHR) and three downregulated (ITGA7, SSTR, and MMP2) genes were identified between TNBC tissue and the luminal subtype of breast cancer tissue. ETV4 messenger ribonucleic acid was more than five-fold upregulated in TNBC tissue compared with the control tissue. ETV4 overexpression was found in 57.0% of 135 TNBC cases. Overexpression of ETV4 protein was associated with an advanced stage and a higher proportion of positive lymph node and lymphovascular invasion. Patients with an ETV4-overexpressed tumor had a significantly higher risk of developing distant metastasis (P<0.0001) and shorter overall survival and disease-free survival. Overexpression of ETV4 protein was an independent predictor of short disease-free survival of TNBC patients (P=0.021).
  
  
  CONCLUSIONS
  Overexpression of ETV4 protein increases risk of developing distant metastasis and results in a poor prognosis for TNBC patients. Thus, ETV4 might be a novel target for developing an alternative therapeutic strategy for prevention of TNBC distant metastasis.
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China ; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Zhong-Yu
authors.initials: ZY
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China ; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Shu-Sen
authors.initials: SS
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China ; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Rou-Jun
authors.initials: RJ
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China ; Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
authors.forename: Li-Bing
authors.initials: LB
authors.lastname: Song
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China ; Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
keywords: ETS translocation variant 4; ETV4; breast carcinoma; prognosis; triple-negative