Uridine-cytidine kinase 2 as a novel potential prognostic and therapeutic biomarker in gastric cancer.

[BACKGROUND] Gastric cancer (GC) is one of the most prevalent and lethal malignancies worldwide, with its high mortality rate attributed to late diagnosis, limited prognostic stratification tools, and a lack of targeted therapeutic options. This study aimed to explore the biological functions and molecular mechanism of uridine-cytidine kinase 2 (UCK2) in GC to identify powerful diagnostic, prognostic, and therapeutic biomarkers for GC.

[METHODS] We systematically analyzed the expression pattern of UCK2 across multiple datasets, including The Cancer Genome Atlas (TCGA) GC cohort, Gene Expression Omnibus (GEO) datasets, and a prospectively collected cohort of GC patients from Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) (comprising matched tumor and normal adjacent tissues). We then examined the biological roles of UCK2 and . A downstream gene expression analysis was performed to explore the potential mechanism of UCK2.

[RESULTS] The results showed that UCK2 expression was higher in the GC tissues than in the non-tumor tissues in TCGA and GEO datasets, and in the cohort of patients from our center. The high expression of UCK2 was closely correlated with more malignant features, such as an advanced pathological T (pT) stage (P=0.02), pathological N (pN) stage (P=0.03), and larger tumor size (P=0.01). The univariate and multivariate Cox regression analyses showed that UCK2 expression level was an independent prognostic factor (hazard ratio: 1.524, 95% confidence interval: 1.039-2.234, P=0.03). Functionally, UCK2 down-regulation or knockout significantly attenuated the proliferation, colony formation, and motility capacity of GC cells . Meanwhile, the silencing of UCK2 inhibited xenograft tumor growth . Mechanistically, the knock-down/knock-out of UCK2 might decrease the expression levels of the p-AKT, cyclin D1, and cyclin E1 proteins in GC cells, leading to G1/S phase arrest.

[CONCLUSIONS] Our findings established UCK2 as a novel and clinically valuable biomarker, providing a potential tool for improving the diagnosis and prognosis evaluation of GC, and highlighted its potential as a therapeutic target for future anti-tumor strategies.