Predicting outcomes for children with neuroblastoma using a multigene-expression signature: a retrospective SIOPEN/COG/GPOH study

Joëlle Vermeulen, Katleen De Preter, Arlene Naranjo, Liesbeth Vercruysse, Nadine Van Roy, Jan Hellemans, Katrien Swerts, Sophie Bravo, Paola Scaruffi, Gian Paolo Tonini, Bruno De Bernardi, Rosa Noguera, Marta Piqueras, Adela Cañete, Victoria Castel, Isabelle Janoueix-Lerosey, Olivier Delattre, Gudrun Schleiermacher, Jean Michon, Valérie CombaretMatthias Fischer, André Oberthuer, Peter F. Ambros, Klaus Beiske, Jean Bénard, Bárbara Marques, Hervé Rubie, Janice Kohler, Ulrike Pötschger, Ruth Ladenstein, Michael D. Hogarty, Patrick McGrady, Wendy B. London, Geneviève Laureys, Frank Speleman, Jo Vandesompele

Research output: Contribution to journalArticlepeer-review

Abstract

Background: More accurate prognostic assessment of patients with neuroblastoma is required to better inform the choice of risk-related therapy. The aim of this study is to develop and validate a gene-expression signature to improve outcome prediction. Methods: 59 genes were selected using an innovative data-mining strategy, and were profiled in the largest neuroblastoma patient series (n=579) to date using real-time quantitative PCR starting from only 20 ng of RNA. A multigene-expression signature was built using 30 training samples, tested on 313 test samples, and subsequently validated in a blind study on an independent set of 236 tumours. Findings: The signature has a performance, sensitivity, and specificity of 85·4% (95% CI 77·7-93·2), 84·4% (66·5-94·1), and 86·5% (81·1-90·6), respectively, to predict patient outcome. Multivariate analysis indicates that the signature is a significant independent predictor of overall survival and progression-free survival after controlling for currently used risk factors: patients with high molecular risk have a higher risk of death from disease and higher risk of relapse or progression than patients with low molecular risk (odds ratio 19·32 [95% CI 6·50-57·43] and 3·96 [1·97-7·97] for overall survival and progression-free survival, respectively, both p

Original languageEnglish
Pages (from-to)663-671
Number of pages9
JournalThe Lancet Oncology
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 2009

ASJC Scopus subject areas

  • Oncology

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