Li Peng, Sun Tingting, Yuan Qingzhong, Pan Guozheng, Zhang Jian, Sun Diwen
Department of Breast and Thyroid Surgery.
Department of Clinical Laboratory, Shengli Oilfield Central Hospital, Dongying, Shandong, People's Republic of China.
Onco Targets Ther. 2016 Sep 19;9:5751-5759. doi: 10.2147/OTT.S113768. eCollection 2016.
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.
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.
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 (<0.001, both). Comparison of features between TNBC and non-TNBC groups showed that histological type (=0.026) and lymph node metastasis (=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 (<0.05). In addition, the enhanced NEDD9 expression was significantly associated with a reduced 5-year survival for TNBC patients (overall survival [OS]: =0.013; disease-free survival [DFS]: =0.021). Negative E-cadherin expression showed a significantly worse 5-year OS and DFS (OS: =0.011; DFS: =0.012). Multivariate analysis showed that lymph node metastasis (OS: =0.006; DFS: =0.004), tumor-node-metastasis stage (OS: =0.012; DFS: =0.001), NEDD9 (OS: =0.046; DFS: =0.022), and E-cadherin (OS: =0.022; DFS: =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: =0.004; DFS: =0.001).
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.
神经前体细胞表达、发育下调基因9（NEDD9）是Crk相关底物家族成员，参与癌细胞黏附、迁移、侵袭及上皮-间质转化。E-钙黏蛋白是上皮-间质转化机制中细胞侵袭的关键事件。本研究旨在评估三阴性乳腺癌（TNBC）患者中NEDD9表达、E-钙黏蛋白表达与生存之间的关联。
采用免疫组织化学法分析106例TNBC患者和120例非TNBC患者的NEDD9和E-钙黏蛋白表达。并采用Kaplan-Meier分析和Cox回归分析TNBC患者临床病理因素与生存的关联。
结果显示，TNBC组中NEDD9表达增加和E-钙黏蛋白表达降低的发生率显著高于非TNBC组（均<0.001）。TNBC组与非TNBC组特征比较显示，组织学类型（=0.026）和淋巴结转移（=0.001）有显著差异。相关性分析显示，NEDD9阳性表达和E-钙黏蛋白阴性表达与淋巴结转移及肿瘤-淋巴结-转移分期显著相关（<0.05）。此外，NEDD9表达增强与TNBC患者5年生存率降低显著相关（总生存[OS]：=0.013；无病生存[DFS]：=0.021）。E-钙黏蛋白阴性表达的5年OS和DFS显著更差（OS：=0.011；DFS：=0.012）。多因素分析显示，淋巴结转移（OS：=0.006；DFS：=0.004）、肿瘤-淋巴结-转移分期（OS：=0.012；DFS：=0.001）、NEDD9（OS：=0.046；DFS：=0.022）和E-钙黏蛋白（OS：=0.022；DFS：=0.025）独立预测OS和DFS预后不良。此外，NEDD9阳性/E-钙黏蛋白阴性表达患者的预后明显比其他组差（OS：=0.004；DFS：=0.001）。
我们的研究结果证明了NEDD9和E-钙黏蛋白表达水平作为TNBC患者预后分子标志物和新治疗靶点的潜在价值。
