Prognostic potential and oncogenic effects of UCH-L1 expression in hilar cholangiocarcinoma

Int J Clin Exp Pathol. 2017 Nov 1;10(11):10802-10811. eCollection 2017.

Abstract

Background: UCH-L1 has been implicated to playing a potential role in cancer development and progression. However, UCH-L1's role in hilar cholangiocarcinoma remains unclear.

Methods: The function of UCH-L1 in hilar cholangiocarcinoma was evaluated using human tissues, molecular and cell biology, and animal models, and its prognostic significance was determined according to its impact on patient survival.

Results: In the present study, UCH-L1 was overexpressed in 62.1% of patients with primary hilar cholangiocarcinoma. Overexpression of UCH-L1 is associated with large tumor size, advanced tumor stage, lymph node metastasis, advanced TNM stage, and high CA19-9 levels, and is also correlated with poor survival rates. Silencing of UCH-L1 inhibited proliferation, colony formation of hilar cholangiocarcinoma cells in vitro and suppressed tumor growth of hilar cholangiocarcinoma cells in vivo. We also observed that silencing of UCH-L1 decreased the phosphorylation level of Akt and PCNA in the xenograft experiments.

Discussion: Taken together, these findings suggest that UCH-L1 functions as an oncogene in the development and progression of hilar cholangiocarcinoma. UCH-L1 can serve as an independent prognostic factor and maybe a potential therapeutic target for patients with hilar cholangiocarcinoma.

Keywords: Hilar cholangiocarcinoma; UCH-L1; biomarkers; prognosis.