Show simple item record

dc.contributor.authorFardin, Paolo
dc.contributor.authorBarla, Annalisa
dc.contributor.authorMosci, Sofia
dc.contributor.authorRosasco, Lorenzo Andrea
dc.contributor.authorVerri, Alessandro
dc.contributor.authorVersteeg, Rogier
dc.contributor.authorCaron, Huib N.
dc.contributor.authorMolenaar, Jan J.
dc.contributor.authorOra, Ingrid
dc.contributor.authorEva, Alessandra
dc.contributor.authorPuppo, Maura
dc.contributor.authorVaresio, Luigi
dc.date.accessioned2012-03-21T20:51:19Z
dc.date.available2012-03-21T20:51:19Z
dc.date.issued2010-07
dc.date.submitted2010-02
dc.identifier.issn1476-4598
dc.identifier.urihttp://hdl.handle.net/1721.1/69819
dc.description.abstractBackground Hypoxia is a condition of low oxygen tension occurring in the tumor microenvironment and it is related to poor prognosis in human cancer. To examine the relationship between hypoxia and neuroblastoma, we generated and tested an in vitro derived hypoxia gene signature for its ability to predict patients' outcome. Results We obtained the gene expression profile of 11 hypoxic neuroblastoma cell lines and we derived a robust 62 probesets signature (NB-hypo) taking advantage of the strong discriminating power of the l1-l2 feature selection technique combined with the analysis of differential gene expression. We profiled gene expression of the tumors of 88 neuroblastoma patients and divided them according to the NB-hypo expression values by K-means clustering. The NB-hypo successfully stratifies the neuroblastoma patients into good and poor prognosis groups. Multivariate Cox analysis revealed that the NB-hypo is a significant independent predictor after controlling for commonly used risk factors including the amplification of MYCN oncogene. NB-hypo increases the resolution of the MYCN stratification by dividing patients with MYCN not amplified tumors in good and poor outcome suggesting that hypoxia is associated with the aggressiveness of neuroblastoma tumor independently from MYCN amplification. Conclusions Our results demonstrate that the NB-hypo is a novel and independent prognostic factor for neuroblastoma and support the view that hypoxia is negatively correlated with tumors' outcome. We show the power of the biology-driven approach in defining hypoxia as a critical molecular program in neuroblastoma and the potential for improvement in the current criteria for risk stratification.en_US
dc.description.sponsorshipFoundation KiKaen_US
dc.description.sponsorshipChildren's Neuroblastoma Cancer Foundationen_US
dc.description.sponsorshipSKK Foundationen_US
dc.description.sponsorshipDutch Cancer Societyen_US
dc.language.isoen_US
dc.publisherBioMed Central Ltd.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1186/1476-4598-9-185en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_US
dc.sourceBioMed Centralen_US
dc.titleA biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patientsen_US
dc.typeArticleen_US
dc.identifier.citationFardin, Paolo et al. “A Biology-driven Approach Identifies the Hypoxia Gene Signature as a Predictor of the Outcome of Neuroblastoma Patients.” Molecular Cancer 9.1 (2010): 185.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Center for Biological & Computational Learningen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentMcGovern Institute for Brain Research at MITen_US
dc.contributor.approverRosasco, Lorenzo Andrea
dc.contributor.mitauthorRosasco, Lorenzo Andrea
dc.relation.journalMolecular Canceren_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsFardin, Paolo; Barla, Annalisa; Mosci, Sofia; Rosasco, Lorenzo; Verri, Alessandro; Versteeg, Rogier; Caron, Huib N; Molenaar, Jan J; Øra, Ingrid; Eva, Alessandra; Puppo, Maura; Varesio, Luigien
dc.identifier.orcidhttps://orcid.org/0000-0001-6376-4786
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record