期刊
EBIOMEDICINE
卷 31, 期 -, 页码 182-189出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2018.04.019
关键词
Gene expression signature; Hypoxia; Prognostic biomarker; Prostate cancer; Radiotherapy
资金
- Belfast-Manchester Movember Centre of Excellence [CE013_2-004]
- Prostate Cancer UK [PG14 008 TR2]
- Cancer Research UK Major Centre funding
- Medical Research Council of the UK [G0801525]
- Cancer Research UK [C2094/A11365, 23969]
- CIHR New Investigator Award
- TFRI New Investigator Award
- CIHR Graduate Fellowship
- Movember Foundation [RS2014-01]
- MRC [G0801525] Funding Source: UKRI
- Cancer Research UK [23969] Funding Source: researchfish
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 nicotinamicle 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. (C) 2018 Published by Elsevier B.V.
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