Expression And Clinical Significance Of FOXO3a In Pancreatic Ductal Adenocarcinoma

Objective: To investigate the expression level of FOXO3 a in normal pancreatic tissue and PDAC,to analyze the relationship of their expression with clinicopathological features and prognosis in PDAC patients,and to verify whether FOXO3 a can be used as a molecular marker for diagnosis of PDAC.Provide new ideas and strategies for the diagnosis and treatment of PDAC.Methods:Collecting clinical data and tumor tissues from 61 patients who underwent surgery for pancreatic malignancies in our hospital and Tianjin Medical University Cancer Institute and Hospital and postoperative pathology confirmed as PDAC from January 2013 to December 2016.At the same time,13 cases of normal tissues of the pancreas were collected.The ?2 test was used to compare the expression of FOXO3 a in normal tissues and tumor tissues,and the relationship between the expression of FOXO3 a and the clinicopathological parameters of patients with PDAC was analyzed.Kaplan-Meier method was used to draw survival curves.Log-rank test and Cox proportional hazards regression model were used to analyze the relationship between FOXO3 a expression and clinicopathological features and overall survival(OS).For analysis,statistical difference is defined as P < 0.05.Results:The expression of FOXO3 a in 13 normal pancreatic tissues,seven(53.8%)tissues were negative,and only one(7.7%)was strongly positive,and the remaining five(38.5%)were low expression.Comparing with normal pancreatic tissues,the expression of FOXO3 a was significantly increased in 61 tumor tissues,5(8.2%)were negative,28(45.9%)were strongly positive,and the total positive rate was 91.8%.The staining results were statistically significant(?2 = 13.248,P < 0.001).In addition,there was a statistically significant difference between the expression of FOXO3 a in the tumor tissue and the degree of tumor differentiation and the primary location of the tumor(?2 value and P value were ?2=24.305,P <0.001 and ?2=8.058,P = 0.005).Kaplan-Meier survival curves showed that the overall survival in patients with low FOXO3 a expression was significantly shorter compared with patients with high FOXO3 a expression(P = 0.013).In the univariate analysis,FOXO3 a expression in tumors(P = 0.013),tumor differentiation(P < 0.001),tumor size(P = 0.058),and postoperative adjuvant therapy(P = 0.052)were closely related to the overall survival,moreover,the expression of FOXO3 a and tumor differentiation were statistically significant(P <0.05).Multivariate analysis showed that tumor differentiation and postoperative adjuvant therapy were independent risk factors for PDAC prognosis(P = 0.004 and 0.006,respectively).In addition,we found that in the multivariate analysis of patients who did not receive postoperative adjuvant therapy the expression level of FOXO3 a was significantly correlated with the prognosis(P = 0.008).Conclusions:The expression of FOXO3 a was differently in normal pancreatic tissue and PDAC tissue.The expression of FOXO3 a in PDAC tissues was significantly higher than that in normal pancreatic tissues,and the prognosis of PDAC patients in the high expression group was significantly better than that in the low expression group.It seems indicated that FOXO3 a may be involved in the tumorigenesis and progression of PDAC.The expression of FOXO3 a in tumor tissues may be related to the pathological progression stage,which can be used to judge the biological behavior of PDAC,and it is expected to be a significant indicator for the early diagnosis of tumor and prognosis of patients.