Integrative proteogenomic characterization of Wilms tumor

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 () and Zhixiang Wu ()
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Cheng Cheng: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Li Zhang: Shanghai Jiao Tong University School of Medicine
Xiaofeng Chang: National Center for Children’s Health
Kai Chen: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Tian He: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Jia Shi: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Fan Lv: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Lijia Pan: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Yangkun Wu: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Qianqian Cheng: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Dong Ren: National Center for Children’s Health
Yongli Guo: National Center for Children’s Health
Weiping Zhang: Beijing Children’s Hospital, Capital Medical University
Huanmin Wang: National Center for Children’s Health
Tieliu Shi: East China Normal University
Jing Li: Shanghai Jiao Tong University
Xin Ni: National Center for Children’s Health
Yeming Wu: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Yaqiong Jin: National Center for Children’s Health
Zhixiang Wu: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-62234-7

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