Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers.
AuthorsWinter, Stuart C
Buffa, Francesca M
Miller, Crispin J
Valentine, Helen R
Shah, Ketan A
Cox, Graham J
Corbridge, Rogan J
Homer, Jarrod J
Slevin, Nicholas J
Price, Patricia M
West, Catharine M L
Harris, Adrian L
AffiliationCancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital.
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AbstractAffymetrix 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.
CitationRelation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers. 2007, 67 (7):3441-9 Cancer Res.
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