BTG1 Low Expression in Pancreatic Ductal Adenocarcinoma is Associated with a Poorer Prognosis

Abstract

Objective: BTG1 is a member of the TOB/BTG protein family, which is a transducer of ErbB-2 and TOB2. BTG1 is known to inhibit tumor genesis, but the role of it in pancreatic ductal adenocarcinoma is still unknown. The purpose of this study is to investigate the expression of BTG1 protein in pancreatic ductal adenocarcinoma (PDAC) and to determine its prognostic significance. Methods: Immunohistochemistry is used to determine the protein expression level of BTG1 gene in 79 surgically resected pancreatic ductal adenocarcinoma. Association of BTG1 expression with all the patients’ clinicopathologic parameters was analyzed using statistical software SPSS22.0. The correlations between BTG1 expression and clinicopathological features were evaluated by Pearson’s chi-square (χ2) test, Fisher’s exact test, and Spearman’s rank. Univariate and multivariate Cox regression analyses were used to identify correlations between the immunohistochemical data for BTG1 expression and the clinicopathologic characteristics in pancreatic ductal adenocarcinoma. Kaplan-Meier analysis was used to demonstrate the correlation between overall survival and the expression of BTG1. Results: BTG1 positive expression was observed in 27.8% (22/79) of the PDAC tissues, which was significantly lower than the 58.2% (46/79) of corresponding normal adjacent non-cancerous tissues by immunohistochemical staining (P<0.001). Through the stratified analysis, we found that significant difference of BTG1 expression in PNI (P=0.002), T stage (P=0.000), N stage (P=0.018) and TNM stage (P=0.000). Univariate and multivariate Cox analysis revealed that BTG1 expression status was an independent prognostic factor in pancreatic ductal adenocarcinoma (P=0.027). Moreover, overall survival was better in PDAC cases with positive than negative BTG1 expression (P=0.027). Conclusion: This study demonstrated for the first time that lower expression of BTG1 might be involved in the progression of pancreatic ductal adenocarcinoma, suggesting that BTG1 might be a novel prognostic marker and target for therapy.