Expression of lymphoid enhancer factor-1 in pancreatic ductal adenocarcinoma and its effect on prognosis / 国际肿瘤学杂志

ABSTRACT

Objective:To investigate the expression of lymphoid enhancement factor-1 (LEF-1) in Wnt signaling pathway in pancreatic ductal adenocarcinoma (PDAC) and its significance.Methods:The relative expressions of LEF-1 mRNA in human PDAC cell line PANC-1 and normal pancreatic ductal epithelial cell line HPDE6 were detected by fluorescence quantitative PCR. A total of 45 pancreatic cancer tissue specimens and their corresponding paracancerous tissue specimens were collected from the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Xinjiang Medical University from June 2012 to December 2013. The expressions of LEF-1 in the cancer tissues and paracancerous tissues were detected by immunohistochemistry, and the relationships between LEF-1 expression and clinicopathological characteristics and prognosis of patients were analyzed.Results:Fluorescence quantitative PCR showed that the relative expression level of LEF-1 mRNA in PANC-1 cell line was significantly higher than that in HPDE-6 cell line (2.895±0.485 vs. 1.006±0.126, t=3.056, P<0.001). Immunohistochemical results showed that LEF-1 was highly expressed in 33 cases (73.3%) of cancer tissues, which was higher than that in 12 cases (26.7%) of adjacent tissues, and there was a statistically significant difference ( χ2=14.815, P<0.001). LEF-1 expression was correlated with preoperative carbohydrate antigen (CA) 19-9 level ( P<0.001) and local lymph node metastasis ( P=0.041). Survival analysis showed that the median overall survival (OS) was 22.0 months in patients with PDAC, 19.0 months in patients with high LEF-1 expression ( n=33), 31.0 months in patients with low LEF-1 expression ( n=12), and there was a statistically significant difference ( χ2=5.554, P=0.018). Univariate Cox regression analysis showed that age ( HR=1.962, 95% CI 1.043-3.692, P=0.037), LEF-1 ( HR=2.253, 95% CI 1.097-4.630, P=0.027), and CA19-9 ( HR=2.667, 95% CI 1.258-5.656, P=0.011) were associated with OS. Multivariate Cox regression analysis showed that CA19-9 ( HR=6.431, 95% CI 1.078-38.382, P=0.041), CA125 ( HR=0.151, 95% CI 0.027-0.839, P=0.031), primary tumor size ( HR=8.364, 95% CI 1.925-36.335, P=0.005), LEF-1 ( HR=2.281, 95% CI 1.025-5.075, P=0.043) were independent risk factors affecting the prognosis of PDAC patients. Conclusion:LEF-1 expression is up-regulated in PDAC tissues, which is positively correlated with preoperative CA19-9 level and local lymph node metastasis, and is an independent prognostic factor in patients with PDAC.