Protein regulator of cytokinesis 1 (PRC1) promotes Wilms tumor progression by orchestrating tumor-stromal crosstalk

Wilms tumor (WT) is the most common pediatric renal malignancy and a major cause of cancer-related morbidity in children. Despite advances in multimodal therapy, patients with high-risk histology, relapsed disease, or bilateral WT continue to experience poor survival and long-term treatment-related toxicity. The absence of effective targeted therapies highlights the urgent need to identify new oncogenic drivers and therapeutic vulnerabilities in WT. Using integrative systems biology approaches, including Weighted Gene Co-expression Network Analysis (WGCNA) and survival analysis across TARGET and GEO datasets, we identified Protein Regulator of Cytokinesis 1 (PRC1) as a gene significantly associated with unfavorable prognosis. PRC1, a critical mediator of spindle organization and cytokinesis, has been implicated in multiple adult cancers, yet its role in Wilms tumor remains undefined. We hypothesize that PRC1 drives Wilms tumor progression by dual mechanisms: (1) intrinsically promoting tumor cell proliferation via the beta-catenin/WT1 axis, and (2) extrinsically reprogramming the tumor stroma through paracrine signaling between WT cells and cancer-associated fibroblasts (CAFs). These findings will provide new mechanistic insights into the role of PRC1 in pediatric kidney cancer and may inform future targeted therapeutic strategies to improve outcomes for children with aggressive or refractory Wilms tumors.