title: miRNA profiles as a predictor of chemoresponsiveness in Wilms' tumor blastema.
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.
authors: The National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors: Jenny A
authors: JA
authors: Watson
authors: Kenneth
authors: K
authors: Bryan
authors: Richard
authors: R
authors: Williams
authors: Sergey
authors: S
authors: Popov
authors: Gordan
authors: G
authors: Vujanic
authors: Aurore
authors: A
authors: Coulomb
authors: Liliane
authors: L
authors: Boccon-Gibod
authors: Norbert
authors: N
authors: Graf
authors: Kathy
authors: K
authors: Pritchard-Jones
authors: Maureen
authors: M
authors: O'Sullivan
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D002675:Child, Preschool; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D057285:Precision Medicine; D011379:Prognosis; D012306:Risk; D015854:Up-Regulation; D009396:Wilms Tumor / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D035683:MicroRNAs