ZBP1 as a prognostic biomarker correlated with cell proliferation in clear cell renal cell carcinoma

Abstract

Background: Z-DNA-binding protein 1 (ZBP1) is a critical Z-DNA- and Z-RNA-binding protein. However, its diagnostic and prognostic significance, as well as its functions in clear cell renal cell carcinoma (ccRCC), are not well understood. Materials and methods: Paired and unpaired differential expression analyses of ZBP1 were performed in pan-cancer cells. Receiver operating characteristic (ROC) curves and survival analyses were used to evaluate the clinical significance of ZBP1. Functional enrichment and immune infiltration analyses were used to explore the mechanisms underlying ZBP1 expression. Western blotting, qRT-PCR, CCK-8, and colony formation assays were used to investigate the potential function of ZBP1 in ccRCC cells. Molecular docking was utilized to identify drugs targeting ZBP1. Results: ZBP1 was highly expressed in ccRCC, demonstrating significant diagnostic and prognostic value. ZBP1 mRNA expression correlated with TNM stage, pathologic stage, and histologic grade. Functional enrichment analyses indicated that ZBP1 is involved in multiple immune processes. Moreover, ZBP1 mRNA expression was positively correlated with the infiltrating levels of T cells and cytotoxic cells, and negatively correlated with the infiltrating levels of mast cells and Th17 cells in ccRCC. Biological experiments confirmed that ZBP1 promotes ccRCC cell proliferation. Molecular docking studies identified rucaparib as a potential drug targeting ZBP1. Conclusion: Our research findings suggest that targeting ZBP1 could represent a novel therapeutic approach to inhibit the progression of ccRCC.

Keywords

• ZBP1
• ccRCC
• Prognosis
• Immune infiltration
• Proliferation