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The expressions of NEDD9 and E-cadherin correlate with metastasis and poor prognosis in triple-negative breast cancer patients

View Article: PubMed Central - PubMed

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).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Representative immunohistochemical staining of NEDD9 and E-cadherin in TNBC: (A) Low expression of NEDD9; (B) High Expression of NEDD9 in the cytoplasm of breast carcinoma cells; (C) Negative expression of E-cadherin; and (D) Positive expression of E-cadherin on the membrane of breast carcinoma cells. A, B, C, and D is ×200 magnification.Abbreviations: NEDD9, neural precursor cell expressed, developmentally downregulated 9; TNBC, triple-negative breast cancer.
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f1-ott-9-5751: Representative immunohistochemical staining of NEDD9 and E-cadherin in TNBC: (A) Low expression of NEDD9; (B) High Expression of NEDD9 in the cytoplasm of breast carcinoma cells; (C) Negative expression of E-cadherin; and (D) Positive expression of E-cadherin on the membrane of breast carcinoma cells. A, B, C, and D is ×200 magnification.Abbreviations: NEDD9, neural precursor cell expressed, developmentally downregulated 9; TNBC, triple-negative breast cancer.

Mentions: Immunohistochemical examination showed that NEDD9 was located predominantly in the cytoplasm in the nests of tumor cells and E-cadherin was intensely expressed on the membrane and weakly in the cytoplasm. The different intensities of staining are shown in Figure 1.


The expressions of NEDD9 and E-cadherin correlate with metastasis and poor prognosis in triple-negative breast cancer patients
Representative immunohistochemical staining of NEDD9 and E-cadherin in TNBC: (A) Low expression of NEDD9; (B) High Expression of NEDD9 in the cytoplasm of breast carcinoma cells; (C) Negative expression of E-cadherin; and (D) Positive expression of E-cadherin on the membrane of breast carcinoma cells. A, B, C, and D is ×200 magnification.Abbreviations: NEDD9, neural precursor cell expressed, developmentally downregulated 9; TNBC, triple-negative breast cancer.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036611&req=5

f1-ott-9-5751: Representative immunohistochemical staining of NEDD9 and E-cadherin in TNBC: (A) Low expression of NEDD9; (B) High Expression of NEDD9 in the cytoplasm of breast carcinoma cells; (C) Negative expression of E-cadherin; and (D) Positive expression of E-cadherin on the membrane of breast carcinoma cells. A, B, C, and D is ×200 magnification.Abbreviations: NEDD9, neural precursor cell expressed, developmentally downregulated 9; TNBC, triple-negative breast cancer.
Mentions: Immunohistochemical examination showed that NEDD9 was located predominantly in the cytoplasm in the nests of tumor cells and E-cadherin was intensely expressed on the membrane and weakly in the cytoplasm. The different intensities of staining are shown in Figure 1.

View Article: PubMed Central - PubMed

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).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus