Article

Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers.

Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital.
Cancer Research (impact factor: 7.86). 04/2007; 67(7):3441-9. DOI:10.1158/0008-5472.CAN-06-3322 pp.3441-9
Source: PubMed

ABSTRACT Affymetrix U133plus2 GeneChips were used to profile 59 head and neck squamous cell cancers. A hypoxia metagene was obtained by analysis of genes whose in vivo expression clustered with the expression of 10 well-known hypoxia-regulated genes (e.g., CA9, GLUT1, and VEGF). To minimize random aggregation, strongly correlated up-regulated genes appearing in >50% of clusters defined a signature comprising 99 genes, of which 27% were previously known to be hypoxia associated. The median RNA expression of the 99 genes in the signature was an independent prognostic factor for recurrence-free survival in a publicly available head and neck cancer data set, outdoing the original intrinsic classifier. In a published breast cancer series, the hypoxia signature was a significant prognostic factor for overall survival independent of clinicopathologic risk factors and a trained profile. The work highlights the validity and potential of using data from analysis of in vitro stress pathways for deriving a biological metagene/gene signature in vivo.

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    Article: A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients.
    Paolo Fardin, Annalisa Barla, Sofia Mosci, Lorenzo Rosasco, Alessandro Verri, Rogier Versteeg, Huib N Caron, Jan J Molenaar, Ingrid Ora, Alessandra Eva, Maura Puppo, Luigi Varesio
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    Molecular Cancer 01/2010; 9:185. · 3.99 Impact Factor
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Keywords

10 well-known hypoxia-regulated genes
 
Affymetrix U133plus2 GeneChips
 
available head
 
clinicopathologic risk factors
 
clusters
 
independent prognostic factor
 
minimize random aggregation
 
neck cancer data
 
neck squamous cell cancers
 
original intrinsic classifier
 
profile 59 head
 
published breast cancer series
 
recurrence-free survival
 
significant prognostic factor
 
trained profile
 
vitro stress pathways