Solid tumors of childhood display specific serum microRNA profiles
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Authors
Raby, Katie L
Saini, Harpreet K
Bailey, Shivani
Wool, Sophie V
Tunnacliffe, Jane M
Nicholson, James C
Coleman, Nicholas
Publication Date
2014-11-21Journal Title
Cancer Epidemiology, Biomarkers & Prevention
ISSN
1055-9965
Publisher
American Association for Cancer Research
Volume
24
Pages
350-360
Type
Article
Metadata
Show full item recordCitation
Murray, M., Raby, K. L., Saini, H. K., Bailey, S., Wool, S. V., Tunnacliffe, J. M., Enright, A., et al. (2014). Solid tumors of childhood display specific serum microRNA profiles. Cancer Epidemiology, Biomarkers & Prevention, 24 350-360. https://doi.org/10.1158/1055-9965.EPI-14-0669
Abstract
Background: Serum biomarkers for diagnosis and risk-stratification of childhood solid
tumors would improve the accuracy and timeliness of diagnosis and reduce the need for
invasive biopsies. We hypothesized that differential expression and/or release of
microRNAs by such tumors may be detected as altered serum microRNA profiles.
Methods: We undertook global quantitative RT-PCR microRNA profiling (n=741) on
RNA extracted 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 that the ‘global-mean’
approach was optimal. We generated a panel of six microRNAs that were most stable in
pediatric serum samples and therefore most suitable for normalization of targeted
microRNA qRT-PCR data. Tumor-specific serum microRNA profiles were identified for
each tumor type and selected microRNAs underwent confirmatory testing. We identified a
panel of microRNAs (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 over-expressed in MYCN-amplified high-risk cases (MYCN-NB). We
also derived candidate microRNA panels for non-invasive 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 microRNA profiling in solid tumors of childhood, and
has identified candidate microRNA profiles for prospective testing. Impact: We propose a
new non-invasive method to diagnose childhood solid tumors
Keywords
biomarker, blood, diagnosis, microRNA, MYCN, neuroblastoma, serum
Sponsorship
RCUK, Other
Funder references
Cancer Research UK (13080)
Identifiers
External DOI: https://doi.org/10.1158/1055-9965.EPI-14-0669
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246038
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