Abstract
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.
Original language | English (US) |
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Pages (from-to) | 182-189 |
Number of pages | 8 |
Journal | EBioMedicine |
Volume | 31 |
DOIs | |
State | Published - May 2018 |
Keywords
- Gene expression signature
- Hypoxia
- Prognostic biomarker
- Prostate cancer
- Radiotherapy
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)