Yang Huajun, Zhang Yunxiao, Yao Xianming, Yang Zebin, Lin Feng
Department of Urology, Hangzhou Children's Hospital, Hangzhou, Zhejiang Province, 310000, China.
Department of Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen City, Guangdong Province, 518107, China.
Curr Pharm Biotechnol. 2025 Aug 6. doi: 10.2174/0113892010396845250730075758.
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.
肾母细胞瘤（WT）是一种常见的儿童肾癌，其进展的分子机制尚不清楚。尽管治疗取得了进展，但高危病例的预后仍然不理想，这凸显了对早期诊断和靶向治疗的新型生物标志物的迫切需求。在本研究中，我们通过识别关键枢纽基因并评估其诊断和预后潜力，研究了WT的分子基础。
从基因表达综合数据库（GEO）数据集中识别差异表达基因（DEG），并使用蛋白质-蛋白质相互作用（PPI）网络分析共同基因以找到枢纽基因。进行了包括细胞增殖、集落形成和伤口愈合在内的功能测定，以验证枢纽基因。还进行了预后价值、miRNA相互作用和泛癌表达分析以及药物敏感性评估。
对公开可用的GEO数据集的基因表达数据进行分析后发现，SLC12A3、ADH6、GSTM3和CLCNKB枢纽基因在WT中显著失调。受试者工作特征（ROC）曲线表明，这些枢纽基因具有很强的诊断潜力，在区分WT与正常组织方面具有高敏感性和特异性。此外，这些基因的表达水平与WT患者的总生存期密切相关，表明它们具有预后意义。此外，对潜在miRNA相互作用的分析表明，特定的miRNA可以调节这些枢纽基因，从而促进WT的发病机制。SLC12A3和ADH6过表达的功能研究表明，细胞增殖、集落形成和迁移能力降低，表明它们参与抑制肿瘤进展。
本研究强调了SLC12A3、ADH6、GSTM3和CLCNKB在WT中的关键作用及其作为WT管理中的诊断生物标志物和治疗靶点的潜力。
