Integrative proteogenomic characterization of Wilms tumor
Cheng Cheng, Li Zhang, Xiaofeng Chang, Kai Chen, He Tian, Jia Chuan Shi, Fang 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, Yaqiong Jin, Zhixiang Wu
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. Wilms tumours are the most common malignant kidney tumour type in children, and their low mutational burden has impeded the development of targeted therapies. Here, the authors perform a proteogenomic characterisation of Wilms tumours, revealing molecular subtypes with different clinical features and identifying EHMT2 as a potential prognostic marker and therapeutic target.