28-Gene Hypoxia Signature Validated as Prognostic Biomarker in Localized Prostate Cancer
A 28-gene mRNA signature derived from in vitro hypoxia profiling and in vivo co-expression analysis was validated across eleven independent prostate cancer cohorts. High signature scores predicted biochemical recurrence and metastasis, independent of clinicopathological factors and existing commercial prognostic tests. The signature also predicted benefit from hypoxia-modifying therapy in a bladder cancer trial, supporting its biological relevance.
The original study
Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer.
- Authors
- Yang L, Roberts D, Takhar M, Erho N, Bibby BAS, Thiruthaneeswaran N, et al.
- Journal
- EBioMedicine
- Type
- Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Validation Study
- PMID
- 29729848
Original 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.