Abstract
The current SIOP treatment protocol for Wilms’ tumor involves pre-operative chemotherapy followed by nephrectomy. Not all patients benefit equally from such chemotherapy. The aim of this study was to generate a miRNA profile of chemo resistant blastemal cells in high risk Wilms’ tumors which might serve as predictive markers of therapeutic response at the pre-treatment biopsy stage. We have shown here that unsupervised hierarchical clustering of genome-wide miRNA expression profiles can clearly separate intermediate risk tumors from high risk tumors. A total of 29 miRNAs were significantly differentially expressed between post-treatment intermediate risk and high risk groups, including miRNAs that have been previously linked to chemo resistance in other cancer types. Furthermore, 7 of these 29 miRNAs were already at the pre-treatment biopsy stage differentially expressed between cases ultimately deemed intermediate risk compared to high risk. These miRNA alterations include down-regulation in high risk cases of miR-193a.5p, miR-27a and the up-regulation of miR-483.5p, miR-628.5p, miR-590.5p, miR-302a and miR-367. The demonstration of such miRNA markers at the pre-treatment biopsy stage could permit stratification of patients to more tailored treatment regimens.
Highlights
Wilms’ Tumor, the commonest pediatric renal tumor, arises predominantly in children under 5 years old, and is thought to develop from embryonic kidney cells [1,2]
According to the SIOP protocol, standard management of renal tumors is pre-operative chemotherapy followed by nephrectomy
In most cases of Wilms’ tumor such therapy induces a considerable degree of tumor shrinkage with evidence of necrosis and cellular differentiation, a proportion of cases show lesser volume reduction and retain an abundance of blastemal tissue post-chemotherapy and these are stratified as high-risk blastemal cases and have a poorer prognosis [4]
Summary
Wilms’ Tumor (nephroblastoma), the commonest pediatric renal tumor, arises predominantly in children under 5 years old, and is thought to develop from embryonic kidney cells [1,2]. The current SIOP (Societe Internationale d’Oncologie Paediatrique) protocol for the treatment of Wilms’ Tumor in patients over the age of 6 months includes neoadjuvant chemotherapy followed by nephrectomy [4]. There are currently no means at biopsy stage of identifying which cases will be ‘blastemal’ and so deemed high-risk at nephrectomy. Along with morphologically identified diffusely anaplastic cases [known to be associated with TP53 mutation], blastemal Wilms’ represent the chemo-resistant cohort requiring more intensive adjuvant chemotherapy. Evidence is emerging for the role of miRNAs in both renal development [8] and Wilms’ tumor progression [9]. Given the lack of clear genomic/genetic pointers, our aim was to identify markers of chemo resistance in Wilms’ tumor by miRNA profiling
Sign-in/Register to view highlights & summary 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.
