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Oncol Lett. 2017 Aug;14(2):1265-1274. doi: 10.3892/ol.2017.6297. Epub 2017 Jun 1.

Cul4B is a novel prognostic marker in cholangiocarcinoma.

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Department of Emergency Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012, P.R. China.
Department of Pathology, Shandong University Medical School, Jinan, Shandong 250012, P.R. China.
Department of Vascular Surgery, Shandong Provincial Hospital, Jinan, Shandong 250012, P.R. China.
Department of Pathology, Shandong University Qilu Hospital, Jinan, Shandong 250012, P.R. China.


Cullin 4B (Cul4B), a scaffold protein that assembles the ubiquitin ligase complex, is involved in a wide variety of physiological and developmental processes, such as cell cycle progression, DNA damage response and gene expression regulation. Cul4B is overexpressed in various solid tumors. However, the prognostic value and role of Cul4B in cholangiocarcinoma (CCA) is largely unknown. The present study demonstrated that Cul4B was overexpressed in 21 (26.6%) of 79 patients with intrahepatic CCA, and in 40 (28.6%) of 140 patients with extrahepatic CCA (EHCC). Kaplan-Meier survival analysis suggested that Cul4B expression is an unfavorable prognostic factor in EHCC patients. Notably, Cul4B and epidermal growth factor receptor expression define a subset of CCA patients with poor prognosis. In vitro data indicated that Cul4B promotes the proliferation, migration and invasion of CCA cells. Furthermore, Cul4B expression promotes the epithelial-mesenchymal transition (EMT) process in CCA cells. Finally, Cul4B repressed the expression of the tumor suppressor genes P16 and phosphatase and tensin homolog. Collectively, the results of the present study revealed an important role of Cul4B in CCA with respect to initiating EMT. Cul4B expression may serve as a prognostic marker for patients with EHCC.


cholangiocarcinoma; cullin 4B; epidermal growth factor receptor; epithelial-mesenchymal transition; prognosis

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