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.
Highlights
Biliary tract cancer (BTC), which is the second most common primary hepatobiliary malignancy, arises from the ductal epithelium of the biliary tree and is characterized by increasing incidence and poor prognosis [1,2,3]
These results suggest that Secreted Frizzled-Related Protein-1 (SFRP1) expression is reduced and b-catenin expression is increased in BTC
Significant differences in histological type, lymph node invasion and overall survival rate (P,0.05) were observed for both genes, while the TNM stage was only statistically different for b-catenin, and the differentiation grade and occurrence of metastasis after surgery showed no statistically significant difference (Table 1). These results suggest that the reduced SFRP1 expression and increased b-catenin expression in BTC correlate with the status of the disease
Summary
Biliary tract cancer (BTC), which is the second most common primary hepatobiliary malignancy, arises from the ductal epithelium of the biliary tree and is characterized by increasing incidence and poor prognosis [1,2,3]. Radical surgical resection, chemotherapy or radiation are used as curative treatments for BTC that is diagnosed in early stages. This disease is usually fatal, with most patients diagnosed in advanced stages [1,4,5]. The Wnt signaling pathway plays an important role in embryonic development, cell differentiation and cell proliferation [8], and its role in bile duct development has been established [9]. Wnt proteins are secreted molecules that interact with transmembrane receptors of the frizzled family. B-catenin is the most important component of the Wnt signaling pathway, with its altered localization serving as a marker of pathway activation
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