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

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 aggregatio...

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Published in:	Cancer research (Chicago, Ill.) Vol. 67; no. 7; p. 3441
Main Authors:	Winter, Stuart C, Buffa, Francesca M, Silva, Priyamal, Miller, Crispin, Valentine, Helen R, Turley, Helen, Shah, Ketan A, Cox, Graham J, Corbridge, Rogan J, Homer, Jarrod J, Musgrove, Brian, Slevin, Nick, Sloan, Philip, Price, Pat, West, Catharine M L, Harris, Adrian L
Format:	Journal Article
Language:	English
Published:	United States 01.04.2007
Subjects:	Adult Aged Aged, 80 and over Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Cell Hypoxia - genetics Female Gene Expression Regulation, Neoplastic Head and Neck Neoplasms - genetics Head and Neck Neoplasms - metabolism Humans Male Middle Aged Multigene Family Oligonucleotide Array Sequence Analysis Prognosis RNA, Messenger - biosynthesis RNA, Messenger - genetics RNA, Neoplasm - biosynthesis RNA, Neoplasm - genetics Up-Regulation
ISSN:	0008-5472
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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.
AbstractList	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. 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.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.
Author	Price, Pat West, Catharine M L Sloan, Philip Valentine, Helen R Homer, Jarrod J Corbridge, Rogan J Harris, Adrian L Musgrove, Brian Miller, Crispin Shah, Ketan A Cox, Graham J Winter, Stuart C Turley, Helen Slevin, Nick Buffa, Francesca M Silva, Priyamal
Author_xml	– sequence: 1 givenname: Stuart C surname: Winter fullname: Winter, Stuart C organization: Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital – sequence: 2 givenname: Francesca M surname: Buffa fullname: Buffa, Francesca M – sequence: 3 givenname: Priyamal surname: Silva fullname: Silva, Priyamal – sequence: 4 givenname: Crispin surname: Miller fullname: Miller, Crispin – sequence: 5 givenname: Helen R surname: Valentine fullname: Valentine, Helen R – sequence: 6 givenname: Helen surname: Turley fullname: Turley, Helen – sequence: 7 givenname: Ketan A surname: Shah fullname: Shah, Ketan A – sequence: 8 givenname: Graham J surname: Cox fullname: Cox, Graham J – sequence: 9 givenname: Rogan J surname: Corbridge fullname: Corbridge, Rogan J – sequence: 10 givenname: Jarrod J surname: Homer fullname: Homer, Jarrod J – sequence: 11 givenname: Brian surname: Musgrove fullname: Musgrove, Brian – sequence: 12 givenname: Nick surname: Slevin fullname: Slevin, Nick – sequence: 13 givenname: Philip surname: Sloan fullname: Sloan, Philip – sequence: 14 givenname: Pat surname: Price fullname: Price, Pat – sequence: 15 givenname: Catharine M L surname: West fullname: West, Catharine M L – sequence: 16 givenname: Adrian L surname: Harris fullname: Harris, Adrian L
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/17409455$$D View this record in MEDLINE/PubMed
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Snippet	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...
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SubjectTerms	Adult Aged Aged, 80 and over Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Cell Hypoxia - genetics Female Gene Expression Regulation, Neoplastic Head and Neck Neoplasms - genetics Head and Neck Neoplasms - metabolism Humans Male Middle Aged Multigene Family Oligonucleotide Array Sequence Analysis Prognosis RNA, Messenger - biosynthesis RNA, Messenger - genetics RNA, Neoplasm - biosynthesis RNA, Neoplasm - genetics Up-Regulation
Title	Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers
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