<i>UCK2</i> upregulation might serve as an indicator of unfavorable prognosis of hepatocellular carcinoma

Yu, Shuo; Xu, Li; Guo, Xiaomao; Zhang, Hang; Qin, Renyi; Wang, Ming

doi:10.1002/iub.1941

Cited by 30 publications

(28 citation statements)

References 19 publications

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“…This peculiarity could enable UCK2 as a significant activating agent of nucleoside prodrugs, such as cyclopentenyl cytidine . Current studies have found that UCK2 is overexpressed in several types of cancer tissues and its upregulation is associated with poor progression and prognosis of breast cancer and hepatocellular carcinoma . Our study shows the high expression of UCK2 in lung cancer, especially in the early stages.…”

Section: Introductionsupporting

confidence: 53%

Uridine‐cytidine kinase 2 (UCK2): A potential diagnostic and prognostic biomarker for lung cancer

Jamal

Xie

et al. 2019

Cancer Science

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Lung cancer has the highest morbidity and mortality among all cancers. Discovery of early diagnostic and prognostic biomarkers of lung cancer can greatly facilitate the survival rate and reduce its mortality. In our study, by analyzing Gene Expression Omnibus and Oncomine databases, we found a novel potential oncogene uridine‐cytidine kinase 2 (UCK2), which was overexpressed in lung tumor tissues compared to adjacent nontumor tissues or normal lung. Then we confirmed this finding in clinical samples. Specifically, UCK2 was identified as highly expressed in stage IA lung cancer with a high diagnostic accuracy (area under the receiver operating characteristic curve > 0.9). We also found that high UCK2 expression was related to poorer clinicopathological features, such as higher T stage and N stage and higher probability of early recurrence. Furthermore, we found that patients with high UCK2 expression had poorer first progression survival and overall survival than patients with low UCK2 expression. Univariate and multivariate Cox regression analyses showed that UCK2 was an independent risk factor related with worse DFS and OS. By gene set enrichment analysis, tumor‐associated biological processes and signaling pathways were enriched in the UCK2 overexpression group, which indicated that UCK2 might play a vital role in lung cancer. Furthermore, in cytology experiments, we found that knockdown of UCK2 could suppress the proliferation and migration of lung cancer cells. In conclusion, our study indicated that UCK2 might be a potential early diagnostic and prognostic biomarker for lung cancer.

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Section: Introductionsupporting

confidence: 53%

Uridine‐cytidine kinase 2 (UCK2): A potential diagnostic and prognostic biomarker for lung cancer

Jamal

Xie

et al. 2019

Cancer Science

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“…Consistent with the analyzed results and previous reports 40 , UCK2 up-regulation in HCCs was confirmed in our great number of clinical samples (Fig. 1C-E).…”

Section: Resultssupporting

confidence: 93%

“…Despite the similarity of their catalytic functions, the catalytic efficacy of UCK2 in uridine and cytosine is 15-20 times higher than that of UCK1 38 , suggesting that UCK2 mainly contributes to the salvage pyrimidine-nucleotide biosynthesis. UCK2 up-regulation has been detected in several types of cancers including pancreatic tumor, colorectal cancer, neuroblastoma, breast cancer, and HCCs 28,37,40 . Some recent studies have demonstrated the correlation of UCK2 with poor prognosis of HCCs 40 , but the underlying mechanism by which UCK2 contributes to HCC progression and the metabolic/non-metabolic roles of UCK2 in HCCs are largely undetermined.…”

Section: Introductionmentioning

confidence: 99%

Non-metabolic role of UCK2 links EGFR-AKT pathway activation to metastasis enhancement in hepatocellular carcinoma

et al. 2020

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Up-regulation of Uridine-cytidine kinase 2 (UCK2), a rate-limiting enzyme of the pyrimidine salvage pathway, has been suggested in HCC, but the detailed molecular mechanisms and therapic role of UCK2 remain elusive. Bioinformatic analyses revealed that UCK2 might be a key up-regulated metabolic gene in HCCs. The expressional pattern and prognostic value of UCK2 were further examined in a large number of clinical samples. Functional assays based on site-directed mutagenesis showed that UCK2 promoted cell proliferation in a metabolic manner, but non-catalytically facilitates HCC metastasis. Mechanistically, in response to EGF, UCK2 interacted with EGFR to block EGF-induced EGFR ubiquitination and degradation, which resulted in elevated EGFR-AKT pathway activation and metastasis enhancement in HCCs. Concurrent pharmacological targeting on UCK2 and EGFR showed synergistic effects on HCC treatment. This study disclosed the non-metabolic role of UCK2 and suggested the therapeutic potential of concurrent blocking the metabolic and non-metabolic roles of UCK2 in HCC treatment.

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“…However, the 5-year survival rate of patients with HCC remains low due to the high rates of local recurrence and distant metastasis ( Allemani et al, 2015 ). Several studies have demonstrated that various aberrantly expressed genes can be used to determine HCC prognosis ( Chen et al, 2018b ; Feng et al, 2019 ; Yu et al, 2019 ; Zhu et al, 2019 ). For example, low expression of CTC-297N7.9 is associated with poor prognosis in HCC patients, and could be used as an independent prognostic indicator in HCC patients.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and prognostic values of upregulated SPC25 in patients with hepatocellular carcinoma

Yang

Sun

Song

et al. 2020

PeerJ

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Background Spindle pole body component 25 (SPC25) plays a vital role in many cellular processes, such as tumorigenesis. However, the clinical significance of SPC25 in hepatocellular carcinoma (HCC) has not been investigated. This study aimed to explore the expression patterns of SPC25 in HCC and non-neoplastic tissues and to investigate the diagnostic and prognostic values of SPC25. Method The expression of SPC25 was examined in 374 HCC issues and 50 non-neoplastic tissues from The Cancer Genome Atlas (TCGA) cohort. The diagnostic and prognostic values of SPC25 were analyzed via receiver operating characteristic (ROC) curve and survival analyses, respectively. Univariate and multivariate Cox regression analyses were used to identify the prognostic factors and to establish a nomogram. The diagnostic and prognostic values were further validated in an external cohort from the International Cancer Genome Consortium (ICGC) database. Results The expression of SPC25 in HCC tissues was significantly higher than that in normal tissues in both cohorts (all P < 0.001). The ROC curve analysis indicated that SPC25 expression has high diagnostic value in HCC with area under the curve (AUC) value of 0.969 (95% confidence interval [CI] [0.948–0.984]) and 0.945 (95% CI [0.920–0.965]) for TCGA and ICGC cohorts, respectively. Patients with HCC exhibiting high SPC25 expression were associated with worse prognosis than those exhibiting low SPC25 expression in both cohorts (all P < 0.001). SPC25 was independently associated with overall survival in both cohorts (all P < 0.001). The concordance indices of the nomogram for predicting overall survival in TCGA and ICGC cohorts were 0.647 and 0.805, respectively, which were higher than those of the American Joint Committee on Cancer (AJCC) staging system. Conclusion SPC25 was upregulated in HCC and independently predicted poor overall survival of patients with HCC. Therefore, SPC25 is an effective diagnostic and prognostic biomarker for HCC. An SPC25-based nomogram was more accurate and useful than the AJCC staging system to predict prognosis of HCC.

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

Cited by 30 publications

References 19 publications

Uridine‐cytidine kinase 2 (UCK2): A potential diagnostic and prognostic biomarker for lung cancer

Uridine‐cytidine kinase 2 (UCK2): A potential diagnostic and prognostic biomarker for lung cancer

Non-metabolic role of UCK2 links EGFR-AKT pathway activation to metastasis enhancement in hepatocellular carcinoma

Diagnostic and prognostic values of upregulated SPC25 in patients with hepatocellular carcinoma

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