Wilms tumor (WT) is a common pediatric kidney cancer with unclear molecular mechanisms driving its progression. Despite advancements in treatment, prognosis remains suboptimal for high-risk cases, highlighting the urgent need for novel biomarkers for early diagnosis and targeted therapies. In this study, we investigated the molecular underpinnings of WT by identifying key hub genes and evaluating their diagnostic and prognostic potential. Differentially expressed genes (DEGs) were identified from Gene Expression Omnibus (GEO) datasets, and common genes were analyzed using protein-protein interaction (PPI) networks to find hub genes. Functional assays, including cell proliferation, colony formation, and wound healing, were performed to validate the hub genes. Prognostic value, miRNA interactions, and pan-cancer expression analysis were also conducted, along with drug sensitivity evaluation. Analysis of gene expression data from publicly available GEO datasets revealed that SLC12A3, ADH6, GSTM3, and CLCNKB hub genes were significantly dysregulated in WT. Receiver operating characteristic (ROC) curve demonstrated that these hub genes showed strong diagnostic potential, with high sensitivity and specificity in distinguishing WT from normal tissues. Additionally, the expression levels of these genes were closely associated with the overall survival of WT patients, indicating their prognostic significance. Furthermore, analysis of potential miRNA interactions revealed that specific miRNAs could regulate these hub genes, contributing to the pathogenesis of WT. Functional studies of SLC12A3 and ADH6 overexpression showed reduced cell proliferation, colony formation, and migratory capacity, suggesting their involvement in inhibiting tumor progression. This study emphasizes the critical roles of SLC12A3, ADH6, GSTM3, and CLCNKB in WT and their potential as both diagnostic biomarkers and therapeutic targets in WT management.
Yang et al. (Wed,) studied this question.