ABSTRACT
Objective To investigate the expression of the E3 ubiquitin ligase neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) in pancreatic cancer tissue and its clinical significance. Methods Clinical data were collected from 58 patients who underwent surgical treatment in Xuzhou Central Hospital from January 2017 to December 2019 and were diagnosed with pancreatic ductal adenocarcinoma based on pathological examination. Immunohistochemistry was used to measure the expression of NEDD4-1 in pancreatic cancer tissue samples, and the association between the expression of NEDD4-1 and the clinicopathological features of pancreatic cancer was analyzed. Western blot was used to measure the protein expression level of NEDD4-1 in normal pancreatic ductal epithelial HPDE6-C7 cells and pancreatic cancer SW1990, BxPC-3, and PANC-1 cells. The t -test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for survival analysis. The Cox proportional-hazards regression model was used to investigate the factors associated with prognosis. Results The expression level of NEDD4-1 in pancreatic cancer tissue was significantly higher than that in adjacent tissue (79.31% vs 19.05%, χ 2 =35.614, P < 0.01), and the protein expression of NEDD4-1 in pancreatic cancer cells was significantly higher than that in normal pancreatic ductal epithelial cells ( P < 0.01). In the patients with pancreatic cancer, the expression of NEDD4-1 was associated with distant metastasis ( χ 2 =5.089, P =0.040), tumor differentiation ( χ 2 =9.071, P =0.003), and TNM stage ( χ 2 =8.882, P =0.003). The patients with high NEDD4-1 expression had a significantly shorter mean survival time than those with low expression (13.61±0.95 months vs 22.22±2.20 months, P =0.001). The Cox regression analysis showed that NEDD4-1 expression (hazard ratio [ HR ]=2.312, 95% confidence interval [ CI ]: 1.010-5.295, P =0.047), degree of tumor differentiation ( HR =2.981, 95% CI : 1.556-5.712, P =0.001), and lymph node metastasis ( HR =2.144, 95% CI : 1.155-3.979, P =0.016) were independent risk factors for the prognosis of patients with pancreatic cancer. Conclusion There is a significant increase in the expression of NEDD4-1 in pancreatic cancer tissue and cells, and the high expression of NEDD4-1 is associated with poor prognosis. Therefore, it can be used as a prognostic biomarker and a therapeutic target for pancreatic cancer.