BACKGROUND: Hypoxia is associated with a poor prognosis in prostate cancer. This work aimed to derive and validate a hypoxia-related mRNA signature for localized prostate cancer.
METHOD: Hypoxia genes were identified in vitro via RNA-sequencing and combined with in vivo gene co-expression analysis to generate a signature. The signature was independently validated in eleven prostate cancer cohorts and a bladder cancer phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON).
RESULTS: A 28-gene signature was derived. Patients with high signature scores had poorer biochemical recurrence free survivals in six of eight independent cohorts of prostatectomy-treated patients (Log rank test P < .05), with borderline significances achieved in the other two (P < .1). The signature also predicted biochemical recurrence in patients receiving post-prostatectomy radiotherapy (n = 130, P = .007) or definitive radiotherapy alone (n = 248, P = .035). Lastly, the signature predicted metastasis events in a pooled cohort (n = 631, P = .002). Prognostic significance remained after adjusting for clinic-pathological factors and commercially available prognostic signatures. The signature predicted benefit from hypoxia-modifying therapy in bladder cancer patients (intervention-by-signature interaction test P = .0026), where carbogen and nicotinamide was associated with improved survival only in hypoxic tumours.
CONCLUSION: A 28-gene hypoxia signature has strong and independent prognostic value for prostate cancer patients.
Recommended CitationYang, Lingjian; Roberts, Darren; Takhar, Mandeep; Erho, Nicholas; Bibby, Becky A.S.; Thiruthaneeswaran, Niluja; Bhandari, Vinayak; Cheng, Wei-Chen; Haider, Syed; McCorry, Amy M.B.; McArt, Darragh; Jain, Suneil; Alshalalfa, Mohammed; Ross, Ashley; Schaffer, Edward; Den, Robert; Karnes, R. Jeffrey; Klein, Eric; Hoskin, Peter J.; Freedland, Stephen J.; Lamb, Alastair D.; Neal, David E.; Buffa, Francesca M.; Bristow, Robert G.; Boutros, Paul C.; Davicioni, Elai; Choudhury, Ananya; and West, Catharine M.L., "Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer." (2018). Department of Radiation Oncology Faculty Papers. Paper 103.
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