Loss of Secreted Frizzled-Related Protein-1 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma

Aims: Secreted Frizzled-Related Protein-1 (SFRP1) is a well-known negative regulator of the wingless type (Wnt)-β-catenin pathway and its inactivation plays an important role in the development and progression of many cancers. In this study, we aimed to determine the clinical significance of SFRP1 expression in intrahepatic cholangiocarcinoma (IHCC) and to define the relationship to Wnt-β-catenin pathway.
Methods: Fifty IHCC patients who had liver resection were enrolled in this study. SFRP1 protein expression was examined by immunohistochemistry in tumor tissues. The patients were divided into two groups: SFRP1 positive (n=30) and negative (n=20). Clinicopathological characteristics were analyzed.
Results: SFRP1 significantly correlated with curability (Cur A, B vs. C, p=0.029); and recurrent pattern (intrahepatic vs. extrahepatic, p=0.010). The negative SFRP1 group had significantly poorer prognosis, and 5-year survival rates were 8.1% of the negative SFRP1 group and 44.6% of the positive SFRP1 group, respectively. Moreover, the disease-free survival rate in the negative SFRP1 group was significantly poorer ( p < 0.001). Multivariate analysis revealed that loss of SFRP1served as an independent prognostic factor in IHCC for both overall (HR, 2.923; 95% CI, 1.30-6.56; p=0.009) and disease-free (HR, 2.631; 95% CI, 1.31-5.27; p＝0.006) survival. In addition, SFRP1 expression negatively correlated to β-catenin expression ( p=0.005).
Conclusions: Those results suggested that the loss of SFRP1 could be a poor prognostic factor for IHCC, through the Wnt-β-catenin pathway.

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本論文は, 著者M. Davaadorjの学位論文として提出され, 学位審査・授与の対象となっている。