The Wnt antagonist sFRP1 as a favorable prognosticator in human biliary tract carcinoma.

Abstract

Inactivation of Secreted Frizzled-Related Protein-1 (SFRP1) and overexpression of β-catenin play important roles in the development and progression of a wide range of malignancies. We sought to determine whether the expression of SFRP1 and β-catenin correlates with clinicopathologic parameters in human biliary tract cancer (BTC) and to evaluate the potential roles of these proteins as prognostic indicators. The expression of SFRP1 and β-catenin in 78 patients with BTC and 36 control patients as investigated by immunohistochemistry. A wide variety of statistical parameters were assessed to determine the association between these proteins and the occurrence, clinical features, and overall survival rate in BTC.SFRP1 and β-catenin had an inverse correlation (r = -0.636, P<0.0001) as assessed by Spearman rank analysis, with 52 (66.7%) of the BTC samples negative for SFRP1 expression and 53 (68.0%) positive for β-catenin expression. Expression of each protein was associated with the histological type and lymph node invasion of BTC. A significantly poorer overall survival rate was observed for patients with low SFRP1 expression (P<0.0001) or high β-catenin expression (P = 0.007). SFRP1 expression (P<0.0001), β-catenin expression (P<0.01) and histological type (P<0.01) were correlated with overall survival rate as assessed by univariate analysis; while multivariate analysis suggested that SFRP1 (hazard ratio, 10.514; 95% confidence intervals, 2.381-39.048; P<0.0001) may serve as an independent prognostic factor for BTC. Collectively, these results demonstrate that SFRP1 is a favorable prognostic factor for human BTC and that its expression inversely correlates with that of β-catenin.