Circulating miRNAs as Non-invasive Biomarkers to Predict Aggressive Prostate Cancer After Radical Prostatectomy

Despite marked advancements in prostate cancer management, there remains a significant clinical need in the post-radical-prostatectomy setting. Some patients treated with radical prostatectomy may have a clinically indolent disease, whereas others may be at high risk of recurrence and poor clinical outcomes. There is a clinical need for novel tests that can better identify these patients who are at risk of recurrence. Furthermore, a non-invasive test that does not rely on tumour specimens would allow for monitoring tumour progression over time. We, therefore, looked at whether circulating miRNA isolated from the serum of prostate cancer patients after radical prostatectomy would be able to stratify patients based on their risk category, using the clinicopathological features of Gleason score, pathological T stage, and margin status.

We evaluated circulating miRNA profiles from the serum of post-radical prostatectomy patients at the Sunnybrook Odette Cancer Centre using Nanostring nCounter Technology. Patients were stratified into high- and low-risk categories based on Gleason score, pathological T stage, surgical margin status, and diagnostic PSA. We identified a four-miRNA signature (miR-17, miR-20a, miR-20b, miR-106a) that can distinguish high- and low-risk patients, in addition to their pathological tumour stage¹. High expression of these miRNAs is associated with shorter time to biochemical recurrence in the TCGA dataset. Furthermore, upon in vitro characterization of these miRNAs, we found they confer an aggressive phenotype by increasing proliferation, soft agar colony formation, and clonogenic survival.

To the best of our knowledge, this is the first report on the characterization of circulating miRNAs from the serum of prostate cancer patients after radical prostatectomy, where circulating miRNA expression was directly compared with clinicopathological features before postoperative radiotherapy. This proof-of-principle study shows that circulating miRNAs found in the serum can stratify patients based on their preoperative risk category. Furthermore, these four miRNAs show biological relevance as oncogenic players based on preclinical validation studies. The main limitation of this study is that the follow-up data is not yet mature enough to investigate whether these miRNAs may predict for biochemical recurrence and other cancer control outcomes.

Future studies will focus on elucidating the prognostic value of these miRNAs using mature follow-up data looking at biochemical recurrence, disease progression, and survival outcomes. A tissue-based genomic classifier test, Decipher, has been demonstrated to independently improve prognostication of post-prostatectomy patients, and further improve metastatic risk within the clinical risk groups²_.The potential integration of tissue-based and circulating miRNA-based tests³ within the context of large prospective studies may ultimately improve the personalized management of patients in the post-prostatectomy setting.

Written by: Christianne Hoey, MSc,^1,2 Hansen He, PhD,^2,3 Stanley Liu, PhD, MD, FRCPC^1,2,4
Author Affiliations:
1. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada
2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
3. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
4. Department of Radiation Oncology, University of Toronto, Toronto, Canada

References:
1. Hoey C et al., Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy. Journal of Translational Medicine 2019; 17: 173.
2. Spratt DE et al., Individual Patient-Level Meta-Analysis of the Performance of the Decipher Genomic Classifier in High-Risk Men After Prostatectomy to Predict Development of Metastatic Disease. Journal of Clinical Oncology 2017; 35(18): 1991-1998.
3. Hoey H and Liu SK. Circulating blood miRNAs for prostate cancer risk stratification: miRroring the underlying tumor biology with liquid biopsies. Research and Reports in Urology 2019; 11:29-42.

Read the Abstract

Login