Abstract
Wilms tumor (WT) is the most common childhood renal cancer. Recent findings of mutations in microRNA (miRNA) processing proteins suggest a pivotal role of miRNAs in WT genesis. We performed miRNA expression profiling of 36 WTs of different subtypes and four normal kidney tissues using microarrays. Additionally, we determined the gene expression profile of 28 of these tumors to identify potentially correlated target genes and affected pathways. We identified 85 miRNAs and 2107 messenger RNAs (mRNA) differentially expressed in blastemal WT, and 266 miRNAs and 1267 mRNAs differentially expressed in regressive subtype. The hierarchical clustering of the samples, using either the miRNA or mRNA profile, showed the clear separation of WT from normal kidney samples, but the miRNA pattern yielded better separation of WT subtypes. A correlation analysis of the deregulated miRNA and mRNAs identified 13,026 miRNA/mRNA pairs with inversely correlated expression, of which 2844 are potential interactions of miRNA and their predicted mRNA targets. We found significant upregulation of miRNAs-183, -301a/b and -335 for the blastemal subtype, and miRNAs-181b, -223 and -630 for the regressive subtype. We found marked deregulation of miRNAs regulating epithelial to mesenchymal transition, especially in the blastemal subtype, and miRNAs influencing chemosensitivity, especially in regressive subtypes. Further research is needed to assess the influence of preoperative chemotherapy and tumor infiltrating lymphocytes on the miRNA and mRNA patterns in WT.
Highlights
Wilms tumor (WT), or nephroblastoma, is the most common childhood renal tumor with an overall survival of more than 90% [1]
Following background correction and quantile normalization, the miRNA expression profiles of 36 WTs and four normal kidney samples were used to identify miRNAs differentially expressed between the main WT subtypes, including regressive WT, mixed WT, and blastemal WT, and normal kidney samples
The one blastemal tumor sample that clusters together with the normal kidneys may have had a low percentage of tumor cells, the miRNA profile might be masked by more abundant normal cells in the sample
Summary
Wilms tumor (WT), or nephroblastoma, is the most common childhood renal tumor with an overall survival of more than 90% [1]. 13% of all patients develop a relapse within the first two years after diagnosis [2]. In Europe, the International Society of Paediatric Oncology (SIOP) defined pre-operative chemotherapy as standard treatment, based solely on imaging studies [3,4]. The Children’s Oncology Group (COG) in North America uses molecular markers for further risk stratified treatment, namely the loss of heterozygosity (LOH). For chromosomes 1p and 16q that is associated with an inferior outcome in a small subgroup of patients with WT [6,7,8,9]. A remaining blastema after chemotherapy is a high risk factor and these patients need the same intensive treatment as patients with diffuse anaplasia [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
