Integrative Transcriptomic Profiling of the Wilms Tumor

SIMPLE SUMMARY: The Wilms tumor is the most common kidney cancer in children. This study characterized complete miRNA and mRNA profiles using a comprehensive NGS sequencing approach to identify miRNAs as transcriptome regulators involved in the Wilms tumor. By analyzing two independent groups of kidney samples with matched controls, we identified 43 miRNAs that are independently differentially expressed in the Wilms tumor irrespective of tumor histological type. Our results provide new insights into the role of transcriptomics in the Wilms tumor and identify universal miRNAs as potential biomarkers for early detection and targets for prevention and treatment of the Wilms tumor. ABSTRACT: Our study aimed to identify relevant transcriptomic biomarkers for the Wilms tumor, the most common pediatric kidney cancer, independent of the histological type and stage. Using next-generation sequencing, we analyzed the miRNA profiles of 74 kidney samples, which were divided into two independent groups: fresh frozen tissue and formalin-fixed paraffin-embedded tissue samples. Subsequent mRNA expression profiling and pathway analysis were performed to establish the interplay and potential involvement of miRNAs and mRNA in the Wilms tumor. Comparative analysis, irrespective of post-dissection tissue processing, revealed 41 differentially expressed miRNAs, with 27 miRNAs having decreased expression and 14 miRNAs having increased expression in the Wilms tumor tissue compared to healthy kidney tissue. Among global mRNA transcriptomic profile differences, cross-sectional analysis suggested a limited list of genes potentially regulated by differentially expressed miRNAs in the Wilms tumor. This study identified the comprehensive miRNA and mRNA profile of the Wilms tumor using next-generation sequencing and bioinformatics approach, providing better insights into the pathogenesis of the Wilms tumor. The identified Wilms tumor miRNAs have potential as biomarkers for the diagnosis and treatment of the Wilms tumor, regardless of histological subtype and disease stage.