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Research Highlight | October 16, 2019

Pan-Canadian team identifies two biomarkers that predict prostate cancer aggressiveness and bone metastasis

Members of TFRI’s Canadian Prostate Cancer Biomarker Network (CPCBN) have identified two new biomarkers that can help predict the aggressiveness of prostate cancer, providing key insights that may one day lead to personalized treatments for men diagnosed with this disease.

The discoveries that the proteins p65 and CCN3 indicate cancer aggressiveness were announced in two separate papers and help to bridge a major gap that still exists in prostate cancer research: patient stratification.

“One of the remaining clinical challenges for prostate cancer is the ability to distinguish patients with a higher risk of progression from those who are diagnosed with a more indolent and non-life threatening disease,” explained urologist Dr. Fred Saad, director of prostate cancer research at the Centre de Recherche du Centre Hospitalier de l’Université de Montréal and CPCBN project leader. “These two discoveries provide the pathologists and clinicians with additional markers to help patient risk stratification and aid in therapeutic decision making and aim at optimizing and personalizing patient care in newly diagnosed patients.”

Additionally, both biomarkers show a positive correlation with metastasis to the bone, the most common site of metastasis in prostate cancer, and a main cause of death for men with prostate cancer. 

“Although this is a long-term goal of the project, a better understanding of bone metastasis formation could lead to the identification of specific targets for cancer therapy,” said Dr. Saad.

Shedding new light on the role of p65 and CCN3 as indicators of tumour aggressiveness

According to the first of their papers published in PLoS Medicine (July 2019), if p65 is found in the nucleus of a prostate cancer cell then a cancer is more aggressive.

“Nuclear p65 was previously shown by us and others to be associated with more aggressive prostate cancer (stage, grade, biochemical relapse), and in this paper we validate this finding using the large, independent, multi-centre, TMA-based resource of the CPCBN,” said Dr. Saad.

In addition to this, for the first time, the nuclear frequency of p65 was shown to be associated with two other important clinical endpoints: prostate cancer-specific mortality and the development of bone metastasis.

In the second paper, published in the American Journal of Pathology (April 2019), the team demonstrated that CCN3, a secreted protein with a known role in promoting breast cancer metastasis to bone, also plays a role as a functional mediator in prostate cancer metastasis, and is associated with poor patient prognosis.

The team used two separate cohorts to prove this, both derived from samples gathered by members of the pan-Canadian network.

“The creation of this resource became feasible only because prostate cancer patients agreed to participate in one of the five prostate cancer biobanks of the CPCBN. We are grateful for the tremendous efforts provided by every team in biobanking, resource assembly and distribution,” said Dr. Saad.

Study 1

Validation of the prognostic value of NF-κB p65 in prostate cancer: A retrospective study using a large multi-institutional cohort of the Canadian Prostate Cancer Biomarker Network

Authors

Grosset AA, Ouellet V, Caron C, Fragoso G, Barrès V, Delvoye N, Latour M, Aprikian A, Bergeron A, Chevalier S, Fazli L, Fleshner N, Gleave M, Karakiewicz P, Lacombe L, Lattouf JB, van der Kwast T, Trudel D, Mes-Masson AM, Saad F; Canadian Prostate Cancer Biomarker Network.

Study 2

CCN3/Nephroblastoma Overexpressed Is a Functional Mediator of Prostate Cancer Bone Metastasis That Is Associated with Poor Patient Prognosis

Authors

Dankner M, Ouellet V, Communal L, Schmitt E, Perkins D, Annis MG, Barrès V, Caron C, Mes-Masson AM, Saad F, Siegel PM; Canadian Prostate Cancer Biomarker Network.

Funding

This research was funded by the Terry Fox Research Institute as part of a pan-Canadian initiative named the Canadian Prostate Cancer Biomarker Network.