Construction of a Cancer Stem Cell Marker Genes-Related 22-Gene Signature for Overall Survival Prediction in High-Risk Wilms’ Tumor

<b>Background:</b> This study aimed to investigate the comprehensive expression profile of cancer stem cell (CSC)-related genes and construct a prognostic signature for overall survival (OS) prediction in high-risk Wilms’ tumor (WT). <b>Materials and methods:</b> Gene expression and survival data from 120 high-risk WT cases in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-WT were used. <b>Results:</b> In total, 229 CSC-related genes were found to be significantly dysregulated in WT compared to tumor-adjacent normal tissues, among which 34 were associated with OS. Using LASSO regression, a 22-gene signature was developed, which exhibited excellent performance in 3-, 5-, and 10-year OS predictions (AUC &gt; 0.86). The high-risk score group showed markedly poorer OS compared to the low-risk score group (median separation, HR = 6.41, 95% CI: 3.18–12.92, <i>p</i> = 3.2e − 9). The 22-gene signature was an independent prognostic factor for OS (HR = 5.086, 95% CI: 3.019–8.568, <i>p</i> &lt; 0.001). <b>Conclusion:</b> This study identified a robust prognostic signature that can effectively support OS prediction.