title: Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers.
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.
authors.affiliation: Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Winter
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Buffa
authors.forename: Priyamal
authors.initials: P
authors.lastname: Silva
authors.forename: Crispin
authors.initials: C
authors.lastname: Miller
authors.forename: Helen R
authors.initials: HR
authors.lastname: Valentine
authors.forename: Helen
authors.initials: H
authors.lastname: Turley
authors.forename: Ketan A
authors.initials: KA
authors.lastname: Shah
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Cox
authors.forename: Rogan J
authors.initials: RJ
authors.lastname: Corbridge
authors.forename: Jarrod J
authors.initials: JJ
authors.lastname: Homer
authors.forename: Brian
authors.initials: B
authors.lastname: Musgrove
authors.forename: Nick
authors.initials: N
authors.lastname: Slevin
authors.forename: Philip
authors.initials: P
authors.lastname: Sloan
authors.forename: Pat
authors.initials: P
authors.lastname: Price
authors.forename: Catharine M L
authors.initials: CM
authors.lastname: West
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm