Integration of multi-omics and single-cell analysis reveals ZBP1 as a prognostic biomarker of renal cell carcinoma

Z-DNA binding protein 1 (ZBP1) is a critical factor that induces various forms of cell death and inflammatory responses. However, it has not been comprehensively analyzed in malignancies. The present study aimed to elucidate the oncogenic role of ZBP1 in human malignancies and examine its prospective function in renal cell carcinoma. The pathogenic significance of ZBP1 in malignancies was clarified using a multi-omics analysis and single-cell analysis utilizing bioinformatics methods. The function of ZBP1 in renal cell carcinoma was validated using in vivo and in vitro studies. In this study, we proved that ZBP1 high expression was significantly correlated with worse prognosis in kidney renal clear cell carcinoma and acute myeloid leukemia. Elevated ZBP1 levels correlated with cancer-associated fibroblast invasion. Furthermore, the single-cell analysis revealed that ZBP1 was significantly expressed in CD4+ T cells, CD8+ T cells, and regulatory T cells. ZBP1 may participate in cancer by regulating the inflammatory pathways. Cellular tests demonstrated that downregulating ZBP1 expression significantly inhibited renal cell carcinoma cell proliferation, migration, and invasion. The transplanted tumor model indicated that suppressing ZBP1 expression significantly reduced tumor progression. ZBP1 is a promising biomarker related to the prognosis of pan-cancer, especially renal cell carcinoma.