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Br J Cancer. 2010 Jan 19;102(2):428-35. doi: 10.1038/sj.bjc.6605450.

Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene.

Author information

1
Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. francesca.buffa@imm.ox.ac.uk

Erratum in

  • Br J Cancer. 2010 Sep 7;103(6):929.

Abstract

BACKGROUND:

There is a need to develop robust and clinically applicable gene expression signatures. Hypoxia is a key factor promoting solid tumour progression and resistance to therapy; a hypoxia signature has the potential to be not only prognostic but also to predict benefit from particular interventions.

METHODS:

An approach for deriving signatures that combine knowledge of gene function and analysis of in vivo co-expression patterns was used to define a common hypoxia signature from three head and neck and five breast cancer studies. Previously validated hypoxia-regulated genes (seeds) were used to generate hypoxia co-expression cancer networks.

RESULTS:

A common hypoxia signature, or metagene, was derived by selecting genes that were consistently co-expressed with the hypoxia seeds in multiple cancers. This was highly enriched for hypoxia-regulated pathways, and prognostic in multivariate analyses. Genes with the highest connectivity were also the most prognostic, and a reduced metagene consisting of a small number of top-ranked genes, including VEGFA, SLC2A1 and PGAM1, outperformed both a larger signature and reported signatures in independent data sets of head and neck, breast and lung cancers.

CONCLUSION:

Combined knowledge of multiple genes' function from in vitro experiments together with meta-analysis of multiple cancers can deliver compact and robust signatures suitable for clinical application.

PMID:
20087356
PMCID:
PMC2816644
DOI:
10.1038/sj.bjc.6605450
[Indexed for MEDLINE]
Free PMC Article
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