Abstract |
Microarray-based molecular signatures have not been widely integrated into neuroblastoma diagnostic classification systems due to the complexities of the assay and requirement for high-quality RNA. New digital technologies that accurately quantify gene expression using RNA isolated from formalin-fixed paraffin embedded (FFPE) tissues are now available. In this study, we describe the first use of a high-throughput digital system to assay the expression of genes in an "ultra-high risk" microarray classifier in FFPE high-risk neuroblastoma tumors. Customized probes corresponding to the 42 genes in a published multi-gene neuroblastoma signature were hybridized to RNA isolated from 107 FFPE high-risk neuroblastoma samples using the NanoString nCounter™ Analysis System. For classification of each patient, the Pearson's correlation coefficient was calculated between the standardized nCounter™ data and the molecular signature from the microarray data. We demonstrate that the nCounter™ 42-gene panel sub-stratified the high-risk cohort into two subsets with statistically significantly different overall survival (p = 0.0027) and event-free survival (p = 0.028). In contrast, none of the established prognostic risk markers (age, stage, tumor histology, MYCN status, and ploidy) were significantly associated with survival. We conclude that the nCounter™ System can reproducibly quantify expression levels of signature genes in FFPE tumor samples. Validation of this microarray signature in our high-risk patient cohort using a completely different technology emphasizes the prognostic relevance of this classifier. Prospective studies testing the prognostic value of molecular signatures in high-risk neuroblastoma patients using FFPE tumor samples and the nCounter™ System are warranted.
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Authors | Thomas P Stricker, Andres Morales La Madrid, Alexandre Chlenski, Lisa Guerrero, Helen R Salwen, Yasmin Gosiengfiao, Elizabeth J Perlman, Wayne Furman, Armita Bahrami, Jason M Shohet, Peter E Zage, M John Hicks, Hiroyuki Shimada, Rie Suganuma, Julie R Park, Sara So, Wendy B London, Peter Pytel, Kirsteen H Maclean, Susan L Cohn |
Journal | Molecular oncology
(Mol Oncol)
Vol. 8
Issue 3
Pg. 669-78
(May 2014)
ISSN: 1878-0261 [Electronic] United States |
PMID | 24560446
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Validation Study)
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Copyright | Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. |
Topics |
- Cluster Analysis
- Cohort Studies
- Gene Expression Profiling
(instrumentation)
- Humans
- Infant
- Neuroblastoma
(diagnosis, genetics)
- Oligonucleotide Array Sequence Analysis
(instrumentation)
- Prognosis
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