Skip to main content
Open Access Publications from the University of California


UCLA Previously Published Works bannerUCLA

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

  • Author(s): Yang, Lingjian;
  • Roberts, Darren;
  • Takhar, Mandeep;
  • Erho, Nicholas;
  • Bibby, Becky AS;
  • Thiruthaneeswaran, Niluja;
  • Bhandari, Vinayak;
  • Cheng, Wei-Chen;
  • Haider, Syed;
  • McCorry, Amy MB;
  • McArt, Darragh;
  • Jain, Suneil;
  • Alshalalfa, Mohammed;
  • Ross, Ashley;
  • Schaffer, Edward;
  • Den, Robert B;
  • Jeffrey Karnes, R;
  • 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;
  • West, Catharine ML
  • et al.


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.


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).


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.


A 28-gene hypoxia signature has strong and independent prognostic value for prostate cancer patients.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View