Abstract
BackgroundDeoxycytidine kinase (DCK), an enzyme in the nucleoside biosynthetic pathway, can affect the development of immune cells. However, the relationships between the expression of DCK, patient prognosis, and tumor-infiltrating immune cells (TIICs) in hepatocellular carcinoma (HCC) are still unclear.MethodsThe expression of DCK in HCC was analyzed through the Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The impact of DCK on clinical prognosis was investigated via the Kaplan-Meier plotter and verified in the Gene Expression Profiling Interactive Analysis (GEPIA) databases. The interrelationships between DCK expression and TIICs in HCC were analyzed by the TIMER database. Additionally, the relationship between DCK expression and immune cell gene markers was calculated through TIMER and GEPIA databases.ResultsCompared with the adjacent normal tissues, high expression of DCK was observed in HCC tissues. Also, the higher expression of DCK was correlated to poorer prognosis in HCC patients, and it was associated with decreased survival in those with early stage and grade. Moreover, DCK expression was positively correlated with TIICs, including CD4+ and CD8+ T cells, B cells, monocytes, tumor-associated macrophages (TAMs), M1 and M2 macrophages, neutrophils, natural killer cells, and dendritic cells. Specifically, DCK expression levels were significantly associated with diverse immune gene marker sets, including those of Tregs and exhausted T cells.ConclusionThese findings suggest that DCK expression is correlated with patient outcomes and tumor infiltration cell levels in HCC patients. Additionally, the increased level of DCK was associated with marker genes of Tregs and exhaustion-related inhibitory receptors, suggesting the potential role of DCK in immunosuppression and immune escape. These findings suggest that DCK can function as a potential novel prognostic biomarker and reflect the immune infiltration status in HCC patients.
Highlights
Hepatocellular carcinoma (HCC), one of the major primary hepatic tumors, is the fourth most common cause of cancer-related death worldwide [1]
In order to validate the expression of Deoxycytidine kinase (DCK) between hepatocellular carcinoma (HCC) tissues and adjacent normal tissues, gene expression analysis was analyzed via the Oncomine database
Prognostic values of DCK expression in HCC we investigated the relationship between the DCK expression and prognosis in HCC using the Kaplan-Meier plotter database
Summary
Hepatocellular carcinoma (HCC), one of the major primary hepatic tumors, is the fourth most common cause of cancer-related death worldwide [1]. Deoxycytidine kinase (DCK) is one of the essential enzymes of the nucleoside salvage pathway, and its expression is associated with the resistance to antiviral and anticancer chemotherapeutic agents [6,7,8]. DCK was expressed differently in breast and pancreatic cancers, and the expression levels were associated with patient prognosis in both types [9, 10]. Deoxycytidine kinase (DCK), an enzyme in the nucleoside biosynthetic pathway, can affect the development of immune cells. The relationships between the expression of DCK, patient prognosis, and tumor-infiltrating immune cells (TIICs) in hepatocellular carcinoma (HCC) are still unclear
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