Upregulation of NME4 is associated with progression and poor prognosis in clear cell renal cell carcinoma

Background: Clear cell renal cell carcinoma (ccRCC) is a common and aggressive malignant tumor of the kidney, with a complex pathogenesis involving abnormal expression of multiple genes and signaling pathways. In recent years, the nucleoside diphosphate kinase 4 (NME4) gene has garnered increasing attention due to its critical role in cell proliferation, differentiation, and migration. This study aims to investigate the role of NME4 in ccRCC and its potential as a biomarker and therapeutic target. Methods: In this study, we knocked down the NME4 gene and observed its effects on 786-O cells (a ccRCC cell line). We assessed cell proliferation and migration capacity using clonogenic assays, Ki67 immunofluorescence staining, and cell scratch assays. Additionally, we systematically analyzed the relationship between NME4 expression levels and clinical characteristics and prognosis in ccRCC patients using multiple large-scale public databases and explored its potential mechanisms in tumor immune regulation. Results: Experimental results showed that NME4 knockdown significantly reduced the clonogenic capacity of 786-O cells, with a marked decrease in both the average number and size of clones. Ki67 immunofluorescence staining results further confirmed that NME4 knockdown inhibited the proliferation capacity of ccRCC cells. Cell scratch assay results showed that the wound healing rate of 786-O cells with NME4 knockdown was significantly reduced, indicating that NME4 also plays an important role in cell migration. Multi-database joint analysis results showed that high NME4 expression is closely associated with poor prognosis in ccRCC patients. In immune cell infiltration and signaling pathway enrichment analysis, high NME4 expression was significantly correlated with multiple immune cell infiltration levels and may promote tumorigenesis and progression by enhancing the activity of multiple signaling pathways. Conclusions: NME4 is highly expressed in ccRCC, and its expression levels are significantly associated with patients’ clinical characteristics and survival prognosis. Meanwhile, experimental results indicate its important role in tumorigenesis and progression. NME4 has the potential to serve as a biomarker and therapeutic target for ccRCC.