期刊
BRITISH JOURNAL OF CANCER
卷 102, 期 2, 页码 428-435出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6605450
关键词
hypoxia; gene expression; meta-analysis; distant relapse
类别
资金
- Cancer Research UK
- EU [FP6-IST-026996]
- Oxford NIHR Comprehensive Biomedical Research Centre
- Manchester Experimental Cancer Medicine Centre
- Medical Research Council, UK
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. British Journal of Cancer (2010) 102, 428-435. doi:10.1038/sj.bjc.6605450 www.bjcancer.com (C) 2010 Cancer Research UK
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