UCK2 upregulation might serve as an indicator of unfavorable prognosis of hepatocellular carcinoma
UCK2 upregulation might serve as an indicator of unfavorable prognosis of hepatocellular carcinoma
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DOI：
10.1002/iub.1941
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发表时间：
2019-01-01
期刊：
影响因子：
4.6
通讯作者：
Wang, Ming
中科院分区：
文献类型：
--
作者：
Yu, Shuo;Li, Xu;Wang, Ming
尿苷-胞苷激酶（由UCK 1、UCKL 1和UCK 2编码）催化尿苷和胞苷磷酸化为尿苷一磷酸（UMP）和胞苷一磷酸（CMP）。在这项研究中，使用癌症基因组图谱（TCGA）的数据，我们分析了尿苷-胞苷激酶基因在肝细胞癌（HCC）中的表达谱，其预后价值，以及与其失调相关的表观遗传学改变。结果显示，UCKL 1和UCK 2在HCC组织中显著上调，而UCK 1在癌旁正常组织中无显著上调。与对照组相比，死亡组和复发组中仅UCK 2显著上调。多因素分析证实UCK 2表达增加是总生存期（OS）和无复发生存期（RFS）缩短的独立预后指标（HR：1.760，95% CI：1.398-2.216，P < 0.001）（HR：1.543，95% CI：1.232-1.933，P < 0.001）。两个CpG位点（cg 09277749和cg 21143899）在肝癌组织中的甲基化水平显著低于癌旁正常组织，且与UCK 2表达呈负相关。然而，生存分析显示，只有cg 0927774的高甲基化与HCC患者的OS和RFS较好相关。基于以上发现，我们推断UCK 2上调可能是HCC中有价值的预后标志物。cg 0927774的甲基化状态可能在其表达中起关键作用。(c)2018 IUBMB Life，71（1）：105-112，2019
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. (c) 2018 IUBMB Life, 71(1):105-112, 2019