A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients
Background 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...
| Main Authors: | , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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BioMed Central Ltd.
2012
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| Online Access: | http://hdl.handle.net/1721.1/69819 https://orcid.org/0000-0001-6376-4786 |
| _version_ | 1826212821975695360 |
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| author | Fardin, Paolo Barla, Annalisa Mosci, Sofia Rosasco, Lorenzo Andrea Verri, Alessandro Versteeg, Rogier Caron, Huib N. Molenaar, Jan J. Ora, Ingrid Eva, Alessandra Puppo, Maura Varesio, Luigi |
| author2 | Massachusetts Institute of Technology. Center for Biological & Computational Learning |
| author_facet | Massachusetts Institute of Technology. Center for Biological & Computational Learning Fardin, Paolo Barla, Annalisa Mosci, Sofia Rosasco, Lorenzo Andrea Verri, Alessandro Versteeg, Rogier Caron, Huib N. Molenaar, Jan J. Ora, Ingrid Eva, Alessandra Puppo, Maura Varesio, Luigi |
| author_sort | Fardin, Paolo |
| collection | MIT |
| description | Background
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. |
| first_indexed | 2024-09-23T15:38:47Z |
| format | Article |
| id | mit-1721.1/69819 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:38:47Z |
| publishDate | 2012 |
| publisher | BioMed Central Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/698192022-10-02T03:05:38Z A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients Fardin, Paolo Barla, Annalisa Mosci, Sofia Rosasco, Lorenzo Andrea Verri, Alessandro Versteeg, Rogier Caron, Huib N. Molenaar, Jan J. Ora, Ingrid Eva, Alessandra Puppo, Maura Varesio, Luigi Massachusetts Institute of Technology. Center for Biological & Computational Learning Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Rosasco, Lorenzo Andrea Rosasco, Lorenzo Andrea Background 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. Foundation KiKa Children's Neuroblastoma Cancer Foundation SKK Foundation Dutch Cancer Society 2012-03-21T20:51:19Z 2012-03-21T20:51:19Z 2010-07 2010-02 Article http://purl.org/eprint/type/JournalArticle 1476-4598 http://hdl.handle.net/1721.1/69819 Fardin, 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. https://orcid.org/0000-0001-6376-4786 en_US http://dx.doi.org/10.1186/1476-4598-9-185 Molecular Cancer Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 application/pdf BioMed Central Ltd. BioMed Central |
| spellingShingle | Fardin, Paolo Barla, Annalisa Mosci, Sofia Rosasco, Lorenzo Andrea Verri, Alessandro Versteeg, Rogier Caron, Huib N. Molenaar, Jan J. Ora, Ingrid Eva, Alessandra Puppo, Maura Varesio, Luigi A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients |
| title | A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients |
| title_full | A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients |
| title_fullStr | A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients |
| title_full_unstemmed | A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients |
| title_short | A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients |
| title_sort | biology driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients |
| url | http://hdl.handle.net/1721.1/69819 https://orcid.org/0000-0001-6376-4786 |
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