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Objective:To investigate the expression level of β-catenin and its relationship with clinicopathology and prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of β-catenin mRNA in primary pancreatic cancer cell line and pancreatic ductal epithelial cell line HPDE6-C7 of the healthy. The data of 45 patients with PDAC confirmed by pathology at Xinjiang Medical University Cancer Hospital from June 2012 to December 2013 were retrospectively analyzed. Immunohistochemical method was used to detect the expression level of β-catenin in cancer tissues and adjacent tissues, and the correlation of β-catenin with pathological characteristics of patients with PDAC was analyzed. Cox proportional hazard model was performed to make univariate and multivariate analysis on the influencing factors of overall survival (OS).Results:The relative expression of β-catenin mRNA in primary pancreatic cancer cells was higher than that in HPDE6-C7 cell line [(3.83±0.83) vs. (1.00±0.03)], and the difference was statistically significant ( t = 3.45, P = 0.003). The high expression rate of β-catenin protein in PDAC tissues was higher than that in para-cancer tissues [68.9% (31/45) vs. 28.9% (14/45)], and the difference was statistically significant ( χ2 = 7.50, P = 0.005). The high expression rate of β-catenin protein in PDAC patients with different tumor diameter and TNM staging had statistically significant differences ( P = 0.026, P = 0.036). The median OS time of 45 patients was 22.5 months, and that of high expression of β-catenin protein group in 31 patients was 19 months, that of low expression of β-catenin group in 14 patients was 29 months, and the difference was statistically significant ( P = 0.009). Univariate Cox analysis showed that preoperative carbohydrate antigen199 (CA199) level, tumor diameter, tumor differentiation degree and the expression level of β-catenin protein were influencing factors of OS of patients with PDAC. Multivariate Cox analysis showed that preoperative CA199 ( OR = 9.883, 95% CI 2.815-34.689, P < 0.001), tumor diameter ( OR = 6.117, 95% CI 1.578-24.179, P = 0.009), tumor differentiation degree ( OR = 3.834, 95% CI 1.158-12.697, P = 0.028), the expression level of β-catenin protein ( OR = 0.139, 95% CI 0.045-0.430, P = 0.001) were independent affecting factors of OS of patients with PADC. Conclusions:β-catenin is abnormally highly expressed in PDAC which is correlated with the disease progression of patients and may be a new indicator and therapeutic target of prognosis for PDAC patients.
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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.
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Objective To introduce the competing risk model into outcome prediction of mild cognitive impairment (MCI) of seniors and to explore influencing factors for the prognosis of MCI to Alzheimer' s disease (AD).Methods Data were collected from six follow-up visits to 600 seniors from communities in Taiyuan city,which were conducted at an interval of six months from October 2010 to May 2013.MCI state was defined as the transient state,AD and death before AD as two absorbing states (death before AD in which was regarded as a competing risk event),building the competing risk model to identify the model parameters,and to explore influencing factors on MCI prognosis to AD.In the meantime,the 3-year MCI-AD transition probability was estimated based on the multi-state Markov model.Results Based on screening with the multivariate competing risk model analysis,factors such as higher age (estimate HR=1.56,95％CI:1.01-2.39),female gender (HR=1.72,95％CI:1.02-2.92),higher education(HR=0.64,95％CI:0.41-1.00),reading frequently (HR=0.57,95％CI:0.32-0.99),hypertension (HR=3.43,95％CI:1.08-10.85) and high SBP(HR=1.67,95％CI:1.04-2.66),were statistically significant for transition from MCI to AD in three years.3-year MCI-AD transition probability was 10.7％(95％CI:8.6％-13.2％).Conclusion Age,gender,education,reading and blood pressure were the influencing factors for the prognosis of MCI to AD.Competing risk model was advantageous in studying longitudinal data with multiple potential outcomes.