Publications

Publications

The prognostic significance of combined ERG and androgen receptor expression in patients with prostate cancer managed by androgen deprivation therapy

By:
Contributors: Bryan Donnelly, MD, MSc, FRCSC, Tarek Bismar Research Group

Cancer Biol Ther. 2014 Sep;15(9):1120-8. doi: 10.4161/cbt.29689. Epub 2014 Jun 27.

Huang KC1, Alshalalfa M2, Hegazy SA3, Dolph M1, Donnelly B4, Bismar TA5.

 

Abstract

ERG and androgen receptor (AR) are known to function cooperatively in prostate cancer (PCa) progression. However, the prognostic value of combined ERG and AR expression and potential pathways are not well characterized. We assessed ERG and AR protein expression by immunohistochemistry in a cohort of 312 men with PCa diagnosed by transurethral resection of the prostate (TURP). Patients were divided into those with no prior hormonal treatment (designated as PCa/AdvPCa) vs. those with castrate-resistant PCa (CRPC) undergoing channel TURP to relieve obstructive symptoms. The expression status was correlated with various clinical-pathological parameters. The Swedish watchful-waiting cohort was used for validation and characterization of potential gene signatures associated with ERG and AR.   Patients with combined ERG-positive/AR high expression profile demonstrated higher rates of PCa-specific mortality (PCSM) compared with patients with ERG-negative/AR low in patients with no prior treatment (n = 90, P = 0.032), but this was attenuated in the overall cohort which included the CRPC subgroup (n = 125, P = 0.096). The prognostic significance to PCSM was validated in the Swedish watchful waiting cohort in univariate (HR: 3.3; 95% CI: 1.9-5.6, P = 4.25E-5) and multivariate analysis (HR: 2; 95% CI: 0.97-4.1, P = 0.057), which included Gleason score. ERG/AR overexpression status characterized 152 genes signatures including WNT, PI3K/AKT and chemokine signaling pathways known to be deregulated in PCa. In conclusion, combined ERG/AR overexpression signifies a class of patients at highest-risk of PCSM with specific key genetic alteration likely responsible for disease progression. The prognostic value of combined ERG/AR overexpression and its associated genes should be further investigated as potential prognostic and therapeutic targets in prostate cancer progression.

PubMed

Download PDF

Stay Informed

To stay up to date on all the latest news and publications, subscribe to our newsletter!

Congratulations to first place winner Doug Brown!

Congratulations to PhD grad student Doug Brown for his First Place win at the 2018 University of Alberta Student Falling Walls Lab Competition! Doug’s First Place award also gains him an entry and an all-expenses-paid trip to the highly competitive and prestigious Falling Walls Lab Conference in Berlin, November 8-9, 2018!

Fifteen student presenters pitched their innovative and globally-important research ideas in a short 3 minute presentation to a panel of science and tech-business savvy judges and a large cheering audience on September 19, 2018, at the University of Alberta in a high-stakes “TEDTalk” meets “Dragon’s Den” style. The competition was very strong but Doug gave an inspired speech on breaking down the walls of metastatic cancers using new lipid nanoparticle technology that he is helping to develop during his graduate studies in Dr. John Lewis’ laboratory.

The Sept 19th UofA Falling Walls Lab competition will be featured on Global News on the evening of Sept. 20th, around 6:15 pm. Check it out!

Doug will be taking his pitch to the Falling Walls Lab competition in Berlin, Germany this November where he will compete with many other inspirational students at this international event.

This is doubly exciting for the Lewis lab because John Lewis recently won the UofA Falling Walls Venture competition that was held on Aug 29, 2018 and he will be competing in the Berlin Falling Walls Venture!

Good luck to both Doug and John at the Falling Walls Finale in Berlin!

- Perrin Beatty