Methylation changes and INS-IGF2 expression predict progression in early-stage Wilms tumor

Abstract

Abstract Wilms tumor, the most common pediatric kidney cancer, accounts for 5% of childhood cancers and is classified by stage and histological subtype. Despite high survival rates (80–85%), approximately 15% of patients experience relapse, reducing survival to around 50%. Epigenetic changes, particularly DNA methylation, play a critical role in Wilms tumor pathogenesis. This study investigates the prognostic potential of DNA methylation in stage I and II patients with favorable histology, aiming to identify early relapse biomarkers. Genome-wide methylation was assessed using methylation microarrays in tumor tissues from relapsed patients (n = 9) and those with complete responses (n = 9), alongside normal tissues (n = 3 each). Differentially methylated probes and regions were analyzed, with additional ROC and survival analyses. Real-time PCR was used to measure IGF2 and INS-IGF2 gene expression. The analysis revealed hypomethylation in intergenic regions in remission patients, identifying 14 differentially methylated positions as potential biomarkers. Increased INS-IGF2 expression was associated with relapse, suggesting its role in disease progression. While the study concentrated on stages I and II patients, where relapse rates are lower, this focus inherently led to a smaller sample size. Despite this, the findings provide valuable insights into the potential role of DNA methylation markers for monitoring disease progression and guiding personalized treatment in Wilms tumor patients. Graphical abstract Genome methylation analysis of WT tumor and normal tissues from complete remission and relapse patients revealed 14 differentially methylated probes (DMPs) and three differentially methylated regions (DMRs) in tumor samples between both groups. Most DMPs demonstrated strong predictive performance for overall and event-free survival. RNA expression analysis showed elevated INS-IGF2 levels in relapse tumor tissue, highlighting its role in WT progression.

Keywords

• Wilms tumor
• DNA methylation
• Epigenetic biomarkers
• INS-IGF2 transcript