Overexpression of NEDD9 is Associated with Altered Expression of E-Cadherin, β-Catenin and N-Cadherin and Predictive of Poor Prognosis in non-Small Cell Lung Cancer

Abstract

Neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) is overexpressed in multiple tumor types, where it is thought to regulate tumor cell metastasis and act as a trigger of the epithelial-mesenchymal transition (EMT). Loss of E-cadherin/β-catenin and upregulation of N-cadherin are hallmarks of the EMT. The expression and correlation of NEDD9 with E-cadherin, β-catenin and N-cadherin in lung cancer are poorly characterized. We examined NEDD9, E-cadherin, β-catenin and N-cadherin protein expression in 105 cases of non-small cell lung carcinoma (NSCLC), including 43 cases of squamous cell carcinoma and 62 cases of lung adenocarcinoma, and the corresponding normal lung tissues using immunohistochemistry. NEDD9 was overexpressed in 56.2% (59/105) of the NSCLC samples compared to normal lung tissue. Overexpression of NEDD9 correlated with abnormal expression of E-cadherin, β-catenin and N-cadherin (P < 0.001, P = 0.008 and P = 0.027, respectively). Additionally, overexpression of NEDD9 correlated positively with lymph node metastasis in NSCLC (Chi-square test; P = 0.015). The mean overall survival of NSCLC patients overexpressing NEDD9 (39.10 ± 6.49months) was markedly shorter than patients with normal NEDD9 expression (56.67 ± 7.44months; Log-Rank, P = 0.001). Moreover, for patients with adenocarcinoma or squarmous cell carcinoma, the survival is also dramatically poorer upon overexpression of NEDD9. In multivariate analysis, overexpression of NEDD9 (P = 0.013) and TNM stage (P = 0.001) were significant independent prognostic factors for overall survival in NSCLC. In conclusion, overexpression of NEDD9 correlates with altered expression of EMT markers, increased lymph node metastasis and poorer survival in lung cancer.