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The following is a summary of “Clinical significance and pro-oncogenic function of DBF4 in clear cell renal cell carcinoma,” published in the January 2025 issue of Urology by Chen et al.
Clear cell renal cell carcinoma (ccRCC) is the most common malignant urological tumor, resistant to chemotherapy and radiotherapy, leading to poor outcomes.
Researchers conducted a retrospective study on DBF4 in ccRCC. DBF4, key in DNA replication, could be a potential target for ccRCC treatment.
They utilized external datasets and bioinformatics analyses to assess DBF4 expression, prognostic value, and potential mechanisms in ccRCC. They validated findings with immunohistochemistry (IHC) on clinical samples and investigated DBF4’s impact on ccRCC progression through assays on cell proliferation, apoptosis, cell cycle, migration, invasion, and colony formation. They performed xenograft tumor models after DBF4 knockdown via shRNA.
The results showed that DBF4 was significantly overexpressed in ccRCC tissues compared to adjacent normal tissues. This was confirmed by the IHC analysis of 75 pairs of clinical samples. Kaplan-Meier analysis indicated that high DBF4 expression correlated with a significantly lower 5-year overall survival rate. Multivariate Cox regression analysis identified DBF4 as an independent risk factor. GO and KEGG analyses revealed enrichment in cell division-related terms, while GSEA showed correlations between increased DBF4 expression and activation of cell cycle pathways. In vitro and in vivo experiments demonstrated that DBF4 knockdown suppressed proliferation and migration, inhibited tumor growth, and arrested the cell cycle at G1/G0, mediated by inhibition of MCM2 phosphorylation and cyclin D1 and CDK4 expression.
Investigators found that DBF4 overexpression was linked to poor prognosis in ccRCC. DBF4 was proposed as a potential biomarker and therapeutic target.
Source: bmcurol.biomedcentral.com/articles/10.1186/s12894-025-01694-x
