Validation of a prognostic multi‐gene signature in high‐risk neuroblastoma using the high throughput digital NanoString nCounter™ system

Molecular Oncology - Tập 8 - Trang 669-678 - 2014
Thomas P. Stricker1, Andres Morales La Madrid2, Alexandre Chlenski2, Lisa Guerrero2, Helen R. Salwen2, Yasmin Gosiengfiao3, Elizabeth J. Perlman4, Wayne Furman5, Armita Bahrami6, Jason M. Shohet7, Peter E. Zage7, M. John Hicks8, Hiroyuki Shimada9, Rie Suganuma9, Julie R. Park10,11, Sara So10,11, Wendy B. London12,13, Peter Pytel14, Kirsteen H. Maclean15, Susan L. Cohn2
1Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA
2Department of Pediatrics, Comer Children's Hospital, University of Chicago, Chicago, IL, USA
3Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
4Department of Pathology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
5Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN USA
6Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, USA
7Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA
8Department of Pathology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA
9Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA
10Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA
11Fred Hutchinson Cancer Research Center, Seattle, WA, USA
12Children's Oncology Group Statistics and Data Center, Boston, MA, USA
13Boston Children's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA
14Department of Pathology, Comer Children's Hospital, University of Chicago, Chicago, IL, USA
15Nanostring Technologies, Seattle, WA, USA

Tóm tắt

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.

Tài liệu tham khảo

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Molecular Oncology

Tập 8

669-678

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