Cheng Cheng, Zhang Li, Chang Xiaofeng, Chen Kai, He Tian, Shi Jia, Lv Fan, Pan Lijia, Wu Yangkun, Cheng Qianqian, Ren Dong, Guo Yongli, Zhang Weiping, Wang Huanmin, Shi Tieliu, Li Jing, Ni Xin, Wu Yeming, Jin Yaqiong, Wu Zhixiang
Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nat Commun. 2025 Aug 19;16(1):7715. doi: 10.1038/s41467-025-62234-7.
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.
肾母细胞瘤（WT）是最常见的儿童肾脏恶性肿瘤，与成人癌症相比，其突变负担相对较低，这阻碍了靶向治疗的发展。为了阐明WT的分子格局，我们对WT及肿瘤旁正常肾组织进行了蛋白质组学、磷酸化蛋白质组学、转录组学和全外显子组测序的综合分析。我们的多组学方法揭示了预后遗传改变、不同的分子亚组、免疫微环境特征以及潜在的生物标志物和治疗靶点。基于蛋白质组和转录组的分层识别出具有独特特征的三个分子亚组，与胚胎肾发育不同阶段的不同组织病理学亚型和假定细胞起源相关。值得注意的是，我们将EHMT2鉴定为一种有前景的预后生物标志物和治疗靶点，与表观遗传调控和Wnt/β-连环蛋白通路相关。在这项工作中，我们提供了WT的全面分子特征，为其发病机制提供了有价值的见解，并为未来的治疗发展提供了基础资源。
