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!

Our First Participant!

Thanks to the participation from men with suspected prostate cancer and men diagnosed with prostate cancer, we will be able to measure if our “tests” can reveal the true nature of prostate cancer and if the tests or biomarkers can diagnose prostate cancer and tell us what cancers are more aggressive.

As part of the Alberta Prostate Registry and Biorepository, patients will be entered into our study, in which blood and other samples are collected over time and their health outcomes are recorded over many years. Patients will follow standard medical advice and care through their doctors. Our team collect biospecimens and information related to general health and cancer behavior over time.

Rather than being frightened by the word ‘cancer’, we want to learn how to predict serious and morbid prostate cancer complications well before they happen, so that we can weigh carefully the pros and cons of available treatments.

In the process, we expect to identify new and important advantage points for better therapies to be developed. The word “cancer” may be scary, but what is truly scary is unawareness.

“It makes me very happy to be able to contribute to find better ways to diagnose prostate cancer.”

- Mr. Garcia

Our International Network of Partners

Meeting these ambitious goals will not be possible without the committed engagement of our many partners across Alberta, Canada and the World. Learn more about our Partners.