A panel of 28 hypoxia-related genes has prognostic value for patients with localized prostate cancer. Translating this panel to the clinic has implications for treatment strategies.

Investigators first generated a prostate-cancer-specific hypoxia signature by identifying changes in the regulation of hypoxia-related genes occurring both in vitro and in vivo. The final signature of 28 genes was derived by cross validating the prognostic significance of identified genes. Patients with a high signature score had significantly worse outcomes.

In the validation cohorts, increased signature score was associated with reduced biochemical-recurrence-free (BRF) survival in patients who received radical prostatectomy. For patients who received postprostatectomy plus radiotherapy or radiotherapy alone, the 28-gene signature was also prognostic for BRF survival. The score was useful in predicting benefit from hypoxia modification of radiotherapy in bladder cancer.

In a pooled cohort of patients with prostate cancer for whom metastatic outcome was assessed, the signature was predictive of distant metastatic events. Furthermore, hypoxia score was positively correlated with tumour stage and Gleason score.

This 28-gene signature had better prognostic significance than the Toustrup signature (which was derived from head and neck cancer, and was the only tested published signature to reach borderline significance in two prostate cancer cohorts). Addition of the signature to a 31-loci genomic classifier signature improved the prognostic utility of both scores.

These data show that this signature can be used to identify patients with hypoxic tumours who have poor outcomes, potentially influencing therapy.