Profiling of the serum MiRNAome in pediatric egyptian patients with wilms tumor

Wilms tumor (WT) is a pediatric kidney cancer associated with poor outcomes in patients with unfavorable histological features such as anaplasia. Small noncoding RNAs, such as miRNAs, are known to be involved in WT pathogenesis. However, research on the clinical potential of blood-based miRNAs is limited. This study aimed to profile aberrantly expressed miRNAs in WT serum samples, evaluate their potential to differentiate standard-risk patients with favorable histology from those with anaplastic WTs, and assess their clinical value as minimally invasive biomarkers for WT detection. The study used next-generation sequencing (NGS) to analyze miRNA expressions in serum samples from 37 Egyptian children, including 10 healthy individuals, 14 with non-anaplastic WTs (favorable histology FH-WTs), and 13 with anaplastic WTs (unfavorable histology UnFH-WTs). Functional enrichment analysis was conducted to identify critical pathways and biological processes affected by dysregulated miRNAs, and a network was created for the most promising miRNA-target interactions linked to WT. The study identified a distinct miRNA expression signature of 45 miRNAs (3 upregulated and 42 downregulated) in WT serum samples compared to healthy controls, with 29 miRNAs exclusively dysregulated in FH-WTs and 6 miRNAs dysregulated solely in UnFH-WTs. These dysregulated miRNAs displayed significant enrichment in cancer-related pathways, such as PI3K/AKT, FOXO, and MAPK signaling. In relation to WT clinicopathological features, decreased levels of hsa-miR-2355-3p showed a significant positive correlation with clinical stage (r = 0.6597, p = 0.0006) and WT metastasis (r = 0.439, p = 0.021). The ROC curve analysis revealed that multiple dysregulated miRNAs in WT, specifically has-miR-7-5p, hsa-miR-146a-5p, hsa-miR-378a-3p, and hsa-miR-483-5p, exhibited high diagnostic potential for WT, with AUC values exceeding 0.86. Among WT histopathology types, the hsa-miR-1180-3p showed a 2.3 log2fold difference in expression between UnFH-WTs and FH-WTs, indicating its potential as a biomarker with 92% sensitivity and 85% specificity for identifying UnFH-WTs. Its target genes were enriched in pathways related to cell division and cell cycle regulation. In conclusion, hsa-miR-1180-3p could be a reliable blood-based biomarker for distinguishing WT histopathological types, and further research is needed to validate its clinical value.