Mohamed Fatma S, Jalal Deena, Fadel Youssef M, El-Mashtoly Samir F, Khaled Wael Z, Sayed Ahmed A, Ghazy Mohamed A
Biotechnology Program, Institute of Basic and Applied Science, Egypt-Japan University of Science and Technology, Alexandria, Egypt.
Biochemistry Program, Faculty of Science, Minia University, Minia, Egypt.
Front Mol Biosci. 2024 Oct 15;11:1453562. doi: 10.3389/fmolb.2024.1453562. eCollection 2024.
Wilms tumor (WT) is a pediatric kidney cancer associated with poor outcomes in patients with unfavorable histological features such as anaplasia. Small non-coding 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 ( = 0.6597, = 0.0006) and WT metastasis ( = 0.439, = 0.021). The ROC curve analysis revealed that multiple dysregulated miRNAs in WT, specifically hsa-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.
肾母细胞瘤（WT）是一种儿科肾癌，对于具有间变等不良组织学特征的患者，其预后较差。已知微小RNA（miRNA）等小非编码RNA参与WT的发病机制。然而，关于血液中miRNA临床潜力的研究有限。本研究旨在分析WT血清样本中异常表达的miRNA，评估其区分组织学良好的标准风险患者与间变性WT患者的潜力，并评估其作为WT检测的微创生物标志物的临床价值。该研究使用下一代测序（NGS）分析了37名埃及儿童血清样本中的miRNA表达，其中包括10名健康个体、14名非间变性WT患者（组织学良好的FH-WT）和13名间变性WT患者（组织学不良的UnFH-WT）。进行了功能富集分析，以确定受失调miRNA影响的关键途径和生物学过程，并构建了与WT相关的最有前景的miRNA-靶标相互作用网络。该研究发现，与健康对照相比，WT血清样本中有45种miRNA（3种上调和42种下调）呈现出独特的miRNA表达特征，其中29种miRNA仅在FH-WT中失调，6种miRNA仅在UnFH-WT中失调。这些失调的miRNA在癌症相关途径中显著富集，如PI3K/AKT、FOXO和MAPK信号通路。关于WT的临床病理特征，hsa-miR-2355-3p水平降低与临床分期（r = 0.6597，P = 0.0006）和WT转移（r = 0.439，P = 0.021）呈显著正相关。ROC曲线分析显示，WT中多种失调的miRNA，特别是hsa-miR-7-5p、hsa-miR-146a-5p、hsa-miR-378a-3p和hsa-miR-483-5p，对WT具有较高诊断潜力，AUC值超过0.86。在WT组织病理学类型中，hsa-miR-1180-3p在UnFH-WT和FH-WT之间的表达差异为2.3 log2倍，表明其作为生物标志物识别UnFH-WT的敏感性为92%，特异性为85%。其靶基因在与细胞分裂和细胞周期调控相关的途径中富集。总之，hsa-miR-1180-3p可能是区分WT组织病理学类型的可靠血液生物标志物，需要进一步研究验证其临床价值。
