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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.

Original publication

DOI

10.1158/0008-5472.CAN-06-3322

Type

Journal article

Journal

Cancer Res

Publication Date

01/04/2007

Volume

67

Pages

3441 - 3449

Keywords

Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell, Cell Hypoxia, Female, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, Humans, Male, Middle Aged, Multigene Family, Oligonucleotide Array Sequence Analysis, Prognosis, RNA, Messenger, RNA, Neoplasm, Up-Regulation