Abstract
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.
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Data availability
Availability of the data and materials, through public databases [TCGA (https://www.cancer.gov/ccg/research/genome-sequencing/tcga), GEO (https://www.ncbi.nlm.nih.gov/geo/), TISCH2 (https://tisch.compbio.cn/home/)] and analysis tools are outlined in the Methods section.
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Funding
This research was funded by the National Natural Science Foundation of China (No: 82560514) and the "Medical Excellence Award" funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University.
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C.L. and C.S. designed the experiments; C.L., J.N. and Y.L. performed the experiments; C.L. and J.N. prepared all figures; C.L., J.N., Y.L., C.W. and W.L. analyzed the data; C.S. and B.S. supervised the work; C.L. wrote the manuscript.
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The study received approval from the First Affiliated Hospital of Guangxi Medical University Ethics Committee (Approval No. 2024-S770-01). The written informed consent of the patient and/or their legal guardian was obtained before the tissue specimens were obtained. All animal experiments were conducted under the approval and supervision of the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (approval number: 2024-D0291).
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Li, C., Nong, J., Li, Y. et al. Integration of multi-omics and single-cell analysis reveals ZBP1 as a prognostic biomarker of renal cell carcinoma. Sci Rep (2026). https://doi.org/10.1038/s41598-026-45826-1
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DOI: https://doi.org/10.1038/s41598-026-45826-1
