Relationship and clinicopathological significance of Numb and epithelial-mesenchymal transition related proteins in human pancreatic cancer

Abstract

Objective: To study the relationship and clinicopathological significance of Numb and epithelial-mesenchymal transition related proteins in human pancreatic cancer(PC). Methods: Sixty-three cases of pancreatic cancer tissues were obtained from department of gastrointestinal surgery in the First Hospital of China Medical University from January 2005 to December 2012, all samples were histopathologically proved to be adenocarcinoma. The expressions of Numb, E-cadherin and Vimentin proteins in 63 cases of pancreatic cancer specimens were detected by immunohistochemistry. Western blot and real-time PCR were used to examine the protein and mRNA levels in two pancreatic cancer cell lines. Pearson and chi-squared tests were used to analyze the relationship and clinicopathological characters with PC patients. Kaplan-Meier curve and log rank test were used to estimate the difference of PC patients' survival. Results: The positive rates of Numb, E-cadherin and Vimentin expressions were 46.0%, 41.3% and 28.6%, respectively. Numb expression was negatively associated with tumor size, differentiation and UICC stage(r=-0.310, P=0.010; r=-0.359, P=0.004; r=-0.228, P=0.020), while E-cadherin expression was negatively related with tumor differentiation(r=-0.316, P=0.012). In contrast, Vimentin expression was positively related with pancreatic cancer differentiation and lymph metastasis(r=0.264, P=0.036; r=0.274, P=0.030). Correlation analysis showed Numb had a positive association with E-cad expression(r=0.325, P=0.010), but had no association with Vimentin. Moreover, patients with co-expression of Numb and E-cadherin had a significantly better overall survival in Kaplan-Meier univariate analysis(P=0.046). Immunoblotting and real-time PCR showed that high Numb protein and mRNA levels in BxPC-3 cells were followed with high E-cadherin and low Vimentin expressions, whereas low Numb protein and mRNA levels in PANC-1 cells were followed with low E-cadherin and high Vimentin expressions, respectively. Conclusions: Numb has a positive relationship with E-cadherin in both pancreatic cancer tissues and cells.The interaction between them might participate in the initiation and development of epithelial-mesenchymal transition in pancreatic cancer.