Expression of the immune gene related to energy metabolism (NDRG1) in Wilms' tumor and its correlation with prognosis

Background and objective: This study aimed to investigate the expression of NDRG1 in Wilms' tumor and analyze its correlation with WT prognosis, thereby elucidating its role and potential mechanisms in the onset and progression of WT. Methods: The expression level of NDRG1 was evaluated in the WT TARGET cohort and validated using the GSE138869 cohort. Univariate and multivariate Cox regression analyses, along with decision curve analysis and nomogram construction, were executed for NDRG1. NDRG1's impact on immune infiltration was assessed through ESTIMATE and CIBERSORT algorithms. Furthermore, factors potentially contributing to the down-regulation of NDRG1 expression in WT were identified via cBioPortal and StarBase. Ultimately, the biological function of NDRG1 in WT was investigated using CCK8 assay and Transwell assay. Results: NDRG1 was found to be an energy metabolism-related IRG by differential and intersection analysis. NDRG1 exhibited downregulated expression in WT patients characterized by unfavorable prognosis and advanced clinical stages. Functional enrichment analysis indicated that NDRG1 was associated with pathways related to DNA binding transcription activator, tubulin binding, and glycosaminoglycan binding. GSEA results demonstrated that NDRG1 was associated with pathways such as Nod-like receptor signaling pathway, nucleotide excision repair and DNA replication. Additionally, Low expression of NDRG1 was associated with worse immune microenvironment and correlated with diminished immune cell infiltration alongside an imbalance within the immune system. In vitro, CCK8 and Transwell assays showed that overexpression of NDRG1 inhibited cell proliferation and migration. Conclusion: NDRG1 may serve as a promising prognostic biomarker for WT linked to immune infiltration dynamics.