DTYMK Induces Metastasis and Propagation of Bladder Cancer Cells and Acts as a Predictive Biomarker

Abstract

Background: Bladder cancer (BLCA) is a common malignancy with rising incidence worldwide. The deoxythymidylate kinase (DTYMK) plays a crucial role in the progression of cancers. However, its precise function and significance in the diagnosis of BLCA are yet to be properly explored. This study aimed to elucidate the correlation between DTYMK and BLCA. Methods: The Cancer Genome Atlas Program (TCGA) database was utilized to verify the DTYMK expression. The expression levels of DTYMK in bladder tissues were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis, and immunohistochemistry. Moreover, the relationship between DTYMK and the prognosis of bladder cancer was analyzed using the KM-plotter and Ualcan databases. DTYMK was knocked down in bladder cancer cells by transfecting with a lentivirus vector to investigate the role of DTYMK both in vitro and in vivo. Additional analyses were performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GeneMania online tools to explore the underlying mechanisms in the progression of bladder cancer. Results: DTYMK expression was significantly increased in bladder cancer tissues compared to the paracancerous tissues (p < 0.01) and found associated with the degree of differentiation (p < 0.05), lymph node metastasis (p < 0.01), tumor node metastasis (TNM) stage (p < 0.01), and poor prognosis in bladder cancer patients. Functional studies demonstrated that down-regulation of DTYMK inhibited cell proliferation and migration in vitro and suppressed xenograft tumor formation in vivo (p < 0.01). GO and KEGG results associated DTYMK with certain physiological events, such as neuroactive ligand-receptor interaction and retinol metabolism. Additionally, 20 genes exhibited a synergistic effect and 10 genes showed interaction with DTYMK in bladder cancer. Conclusions: DTYMK expression was significantly increased in bladder cancer cells. The elevated expression was associated with the degree of differentiation, lymph node metastasis, tumor node metastasis (TNM) stage, and poor prognosis in bladder cancer patients. These findings suggest its potential as a novel predictive biomarker. These findings offer evidence for the potential use of DTYMK as a targeted therapy for bladder cancer.