Reduced selenium-binding protein 1 correlates with a poor prognosis in intrahepatic cholangiocarcinoma and promotes the cell epithelial-mesenchymal transition

Am J Transl Res. 2018 Nov 15;10(11):3567-3578. eCollection 2018.

Abstract

Recent studies have found that selenium-binding protein 1 (SBP1) is downregulated in various malignant tumors. Nevertheless, the role of SBP1 in intrahepatic cholangiocarcinoma (ICC) is largely unknown. In the present study, we aimed to explore the clinical significance and biological function of SBP1 in ICC. Western blotting and immunohistochemistry were performed to evaluate SBP1 expression in ICC tissues, and correlations between SBP1 and clinicopathological parameters were further assessed. The prognostic significance of SBP1 in ICC patients was evaluated via Kaplan-Meier and Cox regression analyses. Moreover, we used RBE, a human ICC cell line, to study the effects of SBP1 knockdown on ICC cell proliferation, migration and invasion. Finally, the expression levels of epithelial-mesenchymal transition-related markers, including snail, vimentin, and E-cadherin, were investigated via Western blotting and immunohistochemistry. The results showed that SBP1 expression was significantly downregulated in ICC tumor tissues, especially in tumor tissues from ICC patients with recurrence or tumor vascular invasion, compared with that in peritumoral tissues (all P < 0.05). In addition, the reduction in SBP1 expression was related to microvascular invasion, lymphatic metastasis, and tumor-node-metastasis (TNM) stage (all P < 0.05). Furthermore, the SBP1 expression level was an independent prognostic factor in ICC (P < 0.05). Knockdown of SBP1 resulted in decreased in vitro proliferation, migration and invasion ability. Low SBP1 expression also resulted in the upregulation of mesenchymal markers such as vimentin and snail. In conclusion, SBP1 may be a prognostic indicator for patients with ICC as well as a potential target for ICC treatment.

Keywords: Selenium-binding protein 1; epithelial-mesenchymal transition; intrahepatic cholangiocarcinoma; prognosis.