title: The expressions of NEDD9 and E-cadherin correlate with metastasis and poor prognosis in triple-negative breast cancer patients.
abstract: BACKGROUND
  Neural precursor cell expressed, developmentally downregulated 9 (NEDD9), a member of Crk-associated substrate family, is involved in cancer cell adhesion, migration, invasion, and epithelial-mesenchymal transition. E-cadherin is a key event in the cellular invasion during the epithelial-mesenchymal transition mechanism. The aim of this study was to evaluate the association among NEDD9 expression, E-cadherin expression, and survival in triple-negative breast cancer (TNBC) patients.
  
  
  METHODS
  NEDD9 and E-cadherin expressions were analyzed by immunohistochemistry in 106 TNBC patients and 120 non-TNBC patients. And the association of clinicopathological factors with survival was analyzed using Kaplan-Meier analysis and Cox regression in TNBC patients.
  
  
  RESULTS
  The results revealed that the rate of increased expression of NEDD9 and reduced expression of E-cadherin was significantly higher in TNBC group than that in non-TNBC group (P<0.001, both). Comparison of features between TNBC and non-TNBC groups showed that histological type (P=0.026) and lymph node metastasis (P=0.001) were significantly different. Correlation analysis showed that positive NEDD9 expression and negative E-cadherin expression were significantly correlated with lymph node metastasis and tumor-node-metastasis stage (P<0.05). In addition, the enhanced NEDD9 expression was significantly associated with a reduced 5-year survival for TNBC patients (overall survival [OS]:P=0.013; disease-free survival [DFS]:P=0.021). Negative E-cadherin expression showed a significantly worse 5-year OS and DFS (OS:P=0.011; DFS:P=0.012). Multivariate analysis showed that lymph node metastasis (OS:P=0.006; DFS:P=0.004), tumor-node-metastasis stage (OS:P=0.012; DFS:P=0.001), NEDD9 (OS:P=0.046; DFS:P=0.022), and E-cadherin (OS:P=0.022; DFS:P=0.025) independently predicted a poor prognosis of OS and DFS. Moreover, patients with NEDD9-positive/E-cadherin-negative expression had a significantly worse outcome than other groups (OS:P=0.004; DFS:P=0.001).
  
  
  CONCLUSIONS
  Our finding demonstrated the potential value of NEDD9 and E-cadherin expression levels as prognostic molecular markers and a target for new therapies for TNBC patients.
authors.affiliation: Department of Breast and Thyroid Surgery.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Shengli Oilfield Central Hospital, Dongying, Shandong, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Breast and Thyroid Surgery.
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Breast and Thyroid Surgery.
authors.forename: Guozheng
authors.initials: G
authors.lastname: Pan
authors.affiliation: Department of Breast and Thyroid Surgery.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Breast and Thyroid Surgery.
authors.forename: Diwen
authors.initials: D
authors.lastname: Sun
keywords: E-cadherin; EMT; NEDD9; TNBC; immunohistochemistry; prognosis