UCK2 upregulation might serve as an indicator of unfavorable prognosis of hepatocellular carcinoma.

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.