Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
IUBMB Life. 2019 Jan;71(1):105-112. doi: 10.1002/iub.1941. Epub 2018 Oct 10.
Uridine-cytidine kinases (encoded by UCK1, UCKL1, and UCK2) catalyze the phosphorylation of uridine and cytidine to uridine monophosphate (UMP) and cytidine monophosphate (CMP). In this study, using data from the Cancer Genome Atlas (TCGA), we analyzed the expression profile of uridine-cytidine kinase genes in hepatocellular carcinoma (HCC), their prognostic value, and the epigenetic alterations associated with their dysregulation. Results showed that UCKL1 and UCK2, but not UCK1 were significantly upregulated in HCC tissues than in adjacent normal tissues. Only UCK2 was significantly upregulated in the deceased group and the recurrence group, compared to the control groups. Multivariate analysis confirmed that increased UCK2 expression was an independent prognostic indicator of shorter overall survival (OS) (HR: 1.760, 95% CI: 1.398-2.216, P < 0.001) and recurrence-free survival (RFS) (HR: 1.543, 95% CI: 1.232-1.933, P < 0.001). Two CpG sites (cg09277749 and cg21143899) were significantly hypomethylated in HCC tissues than in adjacent normal tissues and were negatively correlated with UCK2 expression. However, survival analysis showed that only high methylation of cg0927774 was associated with better OS and RFS of HCC patients. Based on the findings above, we infer that UCK2 upregulation might be a valuable prognostic marker in HCC. The methylation of status cg0927774 might play a critical role in its expression. © 2018 IUBMB Life, 71(1):105-112, 2019.
尿苷-胞苷激酶（由 UCK1、UCKL1 和 UCK2 编码）催化尿苷和胞苷磷酸化为尿苷单磷酸（UMP）和胞苷单磷酸（CMP）。在这项研究中，我们使用癌症基因组图谱（TCGA）的数据，分析了尿苷-胞苷激酶基因在肝细胞癌（HCC）中的表达谱、它们的预后价值以及与它们失调相关的表观遗传改变。结果表明，与相邻正常组织相比，HCC 组织中 UCKL1 和 UCK2，但不是 UCK1，显著上调。与对照组相比，只有 UCK2 在死亡组和复发组中显著上调。多变量分析证实，增加的 UCK2 表达是总生存期（OS）（HR：1.760，95%CI：1.398-2.216，P < 0.001）和无复发生存期（RFS）（HR：1.543，95%CI：1.232-1.933，P < 0.001）较短的独立预后指标。与相邻正常组织相比，HCC 组织中的两个 CpG 位点（cg09277749 和 cg21143899）显著低甲基化，并且与 UCK2 表达呈负相关。然而，生存分析表明，只有 cg0927774 的高甲基化与 HCC 患者的更好的 OS 和 RFS 相关。基于上述发现，我们推断 UCK2 的上调可能是 HCC 的有价值的预后标志物。cg0927774 的甲基化状态可能在其表达中起关键作用。© 2018 IUBMB Life，71（1）：105-112，2019。
