Overexpression of UHRF2 in intrahepatic cholangiocarcinoma and its clinical significance.
Overexpression of UHRF2 in intrahepatic cholangiocarcinoma and its clinical significance.
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UHRF2在肝内胆管癌中的过表达及其临床意义
DOI：
10.2147/ott.s149361
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发表时间：
2017
影响因子：
4
通讯作者：
Bai D
中科院分区：
文献类型：
--
作者：
Peng R;Huang X;Zhang C;Yang X;Xu Y;Bai D
具有 PHD 和环指结构域 2 (UHRF2) 的类泛素与肿瘤发生有关。然而，其在肝内胆管癌（ICC）中的作用仍不清楚。本研究参考公共Oncomine数据库分析了UHRF2在多种癌症中的表达情况，并测定了ICC细胞和组织中UHRF2 mRNA和蛋白的水平。然后，通过UHRF2干扰研究了UHRF2在ICC中的作用。此外，在 ICC 细胞和样本中检查了 UHRF2 和 E-钙粘蛋白表达之间的关系。最后，通过 Cox 回归和 Kaplan-Meier 方法对 139 名 ICC 患者中 UHRF2 的预后作用进行了分析。我们发现UHRF2在多种人类癌症以及ICC中过度表达，并且ICC细胞的侵袭、迁移、增殖和抗凋亡受到UHRF2干扰的抑制。此外，ICC细胞中上皮-间质转化相关标志物E-钙粘蛋白上调，这是受UHRF2表达影响的。临床上，UHRF2表达与ICC的微血管侵犯和淋巴转移呈正相关，且UHRF2high组患者的总生存率远低于UHRF2low组患者，且复发率较高。多变量分析显示 UHRF2 过表达是 ICC 的新预后标志物。因此，我们的结果表明，高水平的 UHRF2 可能是 ICC 预后的新预测因子。
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 UHRF2high group had much lower overall survival and higher recurrence rates than patients in the UHRF2low 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.