Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 24, Issue 2, Pages 350-360Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-14-0669
Keywords
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Funding
- Cancer Research UK
- Medical Research Council
- SPARKS
- Children with Cancer UK/Great Ormond Street Hospital Children's Charity
- MRC [MC_EX_G0800464, MC_U105359875] Funding Source: UKRI
- Action Medical Research [2244] Funding Source: researchfish
- Cancer Research UK [13080] Funding Source: researchfish
- Great Ormond Street Hospital Childrens Charity [W1058] Funding Source: researchfish
- Medical Research Council [MC_EX_G0800464, MC_U105359875] Funding Source: researchfish
- Sparks Charity [11CAM01] Funding Source: researchfish
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Background: Serum biomarkers for diagnosis and risk stratification of childhood solid tumors would improve the accuracy/timeliness of diagnosis and reduce the need for invasive biopsies. We hypothesized that differential expression and/or release of microRNAs (miRNAs) by such tumors may be detected as altered serum miRNA profiles. Methods: We undertook global quantitative reverse transcription PCR (qRT-PCR) miRNA profiling (n = 741) on RNA from 53 serum samples, representing 33 diagnostic cases of common childhood cancers plus 20 controls. Technical confirmation was performed in a subset of 21 cases, plus four independent samples. Results: We incorporated robust quality control steps for RNA extraction, qRT-PCR efficiency and hemolysis quantification. We evaluated multiple methods to normalize global profiling data and identified the 'global mean' approach as optimal. We generated a panel of six miRNAs that were most stable in pediatric serum samples and therefore most suitable for normalization of targeted miRNA qRT-PCR data. Tumor-specific serum miRNA profiles were identified for each tumor type and selected miRNAs underwent confirmatory testing. We identified a panel of miRNAs (miR-124-3p/miR-9-3p/miR-218-5p/miR-490-5p/miR-1538) of potential importance in the clinical management of neuroblastoma, as they were consistently highly overexpressed in MYCN-amplified high-risk cases (MYCN-NB). We also derived candidate miRNA panels for noninvasive differential diagnosis of a liver mass (hepatoblastoma vs. combined MYCN-NB/NB), an abdominal mass (Wilms tumor vs. combined MYCN-NB/NB), and sarcoma subtypes. Conclusions: This study describes a pipeline for robust diagnostic serum miRNA profiling in childhood solid tumors, and has identified candidate miRNA profiles for prospective testing. Impact: We propose a new noninvasive method with the potential to diagnose childhood solid tumors. (C) 2014 AACR.
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