Systematic Review: Prognostic Molecular Biomarkers in Wilms Tumors

Area of Science:

• Pediatric Oncology
• Molecular Pathology
• Cancer Genomics

Background:

• Wilms tumor (WT) risk stratification relies on molecular biomarkers.
• Current research focuses on validating biomarkers for risk-adapted treatment strategies in WT.
• Systematic review to assess prognostic value of key molecular biomarkers in WT.

Purpose of the Study:

• To systematically review literature on the prognostic value of molecular biomarkers in Wilms tumors (WT).
• To identify biomarkers for risk stratification in up-front surgery and preoperative chemotherapy settings for WT.
• To guide future risk-adapted treatment strategies in pediatric WT management.

Main Methods:

• Systematic literature review of PubMed and Embase up to January 2025.
• Included studies with ≥50 de novo Wilms tumors (WT).
• Assessed prognostic value of copy number variations (e.g., 1q gain, 1p/16q LOH) and structural variants (e.g., TP53, MYCN).

Main Results:

• 1q gain identified as a negative prognostic factor for event-free survival (EFS) in up-front nephrectomy settings.
• 1p and/or 16q loss of heterozygosity (LOH)/loss are associated with worse EFS and overall survival (OS) in up-front surgery.
• TP53 and MYCN showed adverse prognostic trends in univariate analyses, requiring further validation.

Conclusions:

• 1q gain and 1p/16q LOH/loss are independent prognostic biomarkers in up-front nephrectomy for Wilms tumors.
• Evidence for prognostic biomarkers in preoperative chemotherapy settings remains limited, especially with SIOP protocols.
• Further adequately powered prospective studies are needed to validate molecular biomarkers, particularly in the preoperative chemotherapy context.