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<p>Wilms tumor (WT), the most common pediatric renal malignancy, exhibits a relatively low mutational burden compared to adult cancers, which hinders the development of targeted therapies. To elucidate the molecular landscape of WT, we perform integrative proteomic, phosphoproteomic, transcriptomic, and whole-exome sequencing analyses of WT and normal&#xa0;kidney tissue&#xa0;adjacent to tumor. Our multi-omics approach uncovers prognostic genetic alterations, distinct molecular subgroups, immune microenvironment features, and potential biomarkers and therapeutic targets. Proteome- and transcriptome-based stratification identifies three molecular subgroups with unique signatures, correlating with different histopathological subtypes and putative cellular origins at different stages of embryonic kidney development. Notably, we identify EHMT2 as a promising prognostic biomarker and therapeutic target associated with epigenetic regulation and Wnt/β-catenin pathway. In this work, we provide a comprehensive molecular characterization of WT, offering valuable insights into its pathogenesis and a foundational resource for future therapeutic development.</p>

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Integrative proteogenomic characterization of Wilms tumor

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月19日

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  • Cheng Cheng,
  • Li Zhang,
  • Xiaofeng Chang,
  • Kai Chen,
  • Tian He,
  • Jia Shi,
  • Fan Lv,
  • Lijia Pan,
  • Yangkun Wu,
  • Qianqian Cheng,
  • Dong Ren,
  • Yongli Guo,
  • Weiping Zhang,
  • Huanmin Wang,
  • Tieliu Shi,
  • Jing Li,
  • Xin Ni,
  • Yeming Wu,
  • Yaqiong Jin,
  • Zhixiang Wu

摘要

Wilms tumor (WT), the most common pediatric renal malignancy, exhibits a relatively low mutational burden compared to adult cancers, which hinders the development of targeted therapies. To elucidate the molecular landscape of WT, we perform integrative proteomic, phosphoproteomic, transcriptomic, and whole-exome sequencing analyses of WT and normal kidney tissue adjacent to tumor. Our multi-omics approach uncovers prognostic genetic alterations, distinct molecular subgroups, immune microenvironment features, and potential biomarkers and therapeutic targets. Proteome- and transcriptome-based stratification identifies three molecular subgroups with unique signatures, correlating with different histopathological subtypes and putative cellular origins at different stages of embryonic kidney development. Notably, we identify EHMT2 as a promising prognostic biomarker and therapeutic target associated with epigenetic regulation and Wnt/β-catenin pathway. In this work, we provide a comprehensive molecular characterization of WT, offering valuable insights into its pathogenesis and a foundational resource for future therapeutic development.