Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer.

Research output: Contribution to journalArticle

  • External authors:
  • Lingjian Yang
  • Mandeep Takhar
  • Nicholas Erho
  • Becky A S Bibby
  • Niluja Thiruthaneeswaran
  • Vinayak Bhandari
  • Wei-Chen Cheng
  • Syed Haider
  • Amy M B McCorry
  • Darragh McArt
  • Suneil Jain
  • Mohammed Alshalalfa
  • Ashley Ross
  • Edward Schaffer
  • Robert B Den
  • R Jeffrey Karnes
  • Eric Klein
  • Stephen J Freedland
  • Alastair D Lamb
  • David E Neal
  • Francesca M Buffa
  • Paul C Boutros
  • Elai Davicioni

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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)182-189
Number of pages8
JournalEBioMedicine
Volume31
Early online date23 Apr 2018
DOIs
Publication statusPublished - May 2018

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