Screening of potential hub genes involved in Kidney Wilms tumor via bioinformatics analysis and experimental validation

Abstract

Abstract Background: Wilms tumor (WT) is the most common pediatric embryonal tumor. Improving patient outcomes requires advances in understanding and targeting the multiple genes and cellular control pathways, but its pathogenesis is currently not well-researched. We aimed to identify the potential molecular biological mechanism of WT and develop new prognostic markers and molecular targets by comparing gene expression profiles of Wilms tumors and fetal normal kidneys. Methods: We performed differential gene expression analysis on Wilms tumor transcriptomic data from the GEO database and TARGET database. GO, KEGG, and GSEA pathways were utilized for the biological functional analysis. 9 of 24 hub genes were identified had prognosis-related by univariate Cox regression analysis. Nine genes underwent LASSO regression analysis to enhance the predictive capability of the model. Finally, The key hub genes were validated in the TARGET-WT datasets, and cell function experiments were conducted to identify the gene's function in the WiT-49 cell. Results: The enrichment analysis revealed that DEGs were significantly involved in the regulation of angiogenesis and regulation of cell differentiation. 24 DEGs were identified through PPI networks and the MCODE algorithm, and 9 of 24 genes were related to WT patients' prognosis. EMCN and CCNA1 were identified as key hub genes, and related to the progression of WT. Functionally, over-expression of EMCN and CCNA1 knockdown inhibited cell viability, proliferation, migration, and invasion of Wilms tumor cells. Conclusions Our study suggests that EMCN and CCNA1 as prognostic signatures associated with the progression of WT.