Overexpression of UHRF2 in intrahepatic cholangiocarcinoma and its clinical significance

Rui Peng; Xiaoyong Huang; Chi Zhang; Xuan Yang; Yaping Xu; Dousheng Bai

doi:10.2147/OTT.S149361

Overexpression of UHRF2 in intrahepatic cholangiocarcinoma and its clinical significance

Onco Targets Ther. 2017 Dec 11:10:5863-5872. doi: 10.2147/OTT.S149361. eCollection 2017.

Authors

Rui Peng^#^{1

2}, Xiaoyong Huang^#³, Chi Zhang^#², Xuan Yang^#^{3

4}, Yaping Xu⁵, Dousheng Bai²

Affiliations

¹ The Second Affiliated Hospital of Xiangya School of Medicine, Central South University, Hunan.
² Department of Hepatobiliary and Pancreatic Surgery, Subei People Hospital, Clinical Medical College of Yangzhou University, Jiangsu.
³ Liver Cancer Institute, Zhongshan Hospital.
⁴ Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai.
⁵ Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.

^# Contributed equally.

Abstract

Ubiquitin-like with PHD and ring finger domains 2 (UHRF2) has been implicated in tumorigenesis. However, its roles in intrahepatic cholangiocarcinoma (ICC) are still unclear. In this study, UHRF2 expression was analyzed in several kinds of cancers by referring to public Oncomine database, and the levels of UHRF2 mRNA and protein were determined in ICC cells and tissues. Then, the roles of UHRF2 in ICC were investigated by UHRF2 interference. Moreover, the relationship between UHRF2 and E-cadherin expression was examined in ICC cells and samples. Finally, the prognostic role of UHRF2 in ICC was analyzed in 139 ICC patients by Cox regression and Kaplan-Meier methods. We found UHRF2 was overexpressed in multiple human cancers, as well as in ICC, and the invasion, migration, proliferation, and antiapoptosis of ICC cells were inhibited by UHRF2 interference. Moreover, the epithelial-mesenchymal transition-related marker E-cadherin was upregulated in ICC cells which was influenced by UHRF2 expression. Clinically, UHRF2 expression was positively associated with microvascular invasion and lymphatic metastasis of ICC, and patients in the UHRF2^high group had much lower overall survival and higher recurrence rates than patients in the UHRF2^low group. A multivariate analysis revealed that UHRF2 overexpression was a new prognostic marker for ICC. Thus, our results indicated that high level of UHRF2 might be a novel predictor for the prognosis of ICC.

Keywords: E-cadherin; ICC; UHRF2; biomarker; prognosis.