Relation of a Hypoxia Metagene Derived from Head and Neck Cancer to Prognosis of Multiple Cancers

TLDR

A 99‑gene hypoxia metagene was derived from Affymetrix U133plus2 profiling of 59 head and neck squamous cell cancers by clustering with 10 canonical hypoxia genes and selecting strongly correlated up‑regulated genes present in over half of the clusters. The 99‑gene hypoxia signature independently predicted recurrence‑free survival in head and neck cancer and overall survival in breast cancer, outperforming existing classifiers and underscoring the utility of in‑vitro stress‑pathway data for generating prognostic metagenes. Cancer Res 2007;67(7):3441–9.

Abstract

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. [Cancer Res 2007;67(7):3441–9]