PLoS ONE (Jan 2013)

miRNA profiles as a predictor of chemoresponsiveness in Wilms' tumor blastema.

  • Jenny A Watson,
  • Kenneth Bryan,
  • Richard Williams,
  • Sergey Popov,
  • Gordan Vujanic,
  • Aurore Coulomb,
  • Liliane Boccon-Gibod,
  • Norbert Graf,
  • Kathy Pritchard-Jones,
  • Maureen O'Sullivan

DOI
https://doi.org/10.1371/journal.pone.0053417
Journal volume & issue
Vol. 8, no. 1
p. e53417

Abstract

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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.