Deciphering metastasis in pediatric Wilms' and rhabdoid tumors: IMPA2 as a key molecular player and promising therapeutic target

Wilms' tumor (WT) and rhabdoid tumor (RT) are the predominant renal neoplasms in pediatric patients, and their metastatic potential significantly impacts the prognosis of affected children. However, limited research has been conducted on elucidating the underlying molecular mechanisms driving metastasis in these tumors, resulting in a dearth of well-defined molecular targets. Based on the clinical staging information available in the TARGET database for WT and RT, we investigated the differential gene expression profiles and associated molecular pathways implicated in metastasis. Interestingly, our analysis revealed that WT and RT tumor metastases shared a highly expressed gene IMPA2, which was associated with poor prognosis. Additionally, experimental validation confirmed that IMPA2 exerted regulatory effects on the Wnt signaling pathway as well as N-cadherin and E-cadherin levels, thereby influencing the migratory and invasive capabilities of G401 cells. Moreover, gene profiles and molecular pathways associated with IMPA2 expression were comprehensively analyzed, transcription factors potentially regulating IMPA2 were identified, and correlations with immune-related genes were determined. Regarding therapy, we identified small molecule drugs that affected IMPA2 expression and utilized molecular docking to predict their direct binding to the IMPA2 protein. These findings have provided biomarkers and therapeutic targets for the metastatic WT and RT, while the investigated targeted drugs hold promise as novel therapeutic strategies to enhance the prognosis of affected children.