Patients with hypoxic tumors poorly respond to radiotherapy and could benefit from hypoxia modification during radiotherapy. To identify these tumors, various gene expression profiles characteristic for hypoxic tumors have been suggested.

Published profiles for hypoxia and in vitro obtained gene sets with early and late hypoxia response genes were compared using expression data from 224 head and neck cancer patients from three different datasets. The ability to predict local recurrence after chemoradiotherapy was tested for the different profiles.

Although only 3 genes were similar in the four validated hypoxia profiles, the profiles showed a near complete correlation with each other in categorizing the 224 patients. The published signatures correlated with the in vitro developed late hypoxia response, not with the early hypoxia response genes. Interestingly, the early hypoxia profile better predicted local recurrence after chemoradiotherapy.

Different sets of genes can be used interchangeably to study hypoxia status of tumors. Four published profiles were related to chronic rather than to acute in vitro hypoxia, while the acute profile better predicted local recurrence. For a better prediction of hypoxia status and the risk of recurrence, acute hypoxia profiles should be incorporated into existing models.