A team of TFRI-funded researchers led by Drs. Thomas Kislinger (University of Toronto) and Paul Boutros (UCLA) has created the first-ever resource that maps the complete proteogenomic landscape of localized, intermediate-risk prostate cancers.
Published in Cancer Cell (March 2019), the resource combines genomic, epigenomic, transcriptomic and proteomic data. It was derived from a cohort of 76 prostate cancer patients and provides a series of key insights into the complete biology of their cancers, including:
- The discovery that established genomic subtypes of prostate cancer converge on five proteomic subtypes, which are themselves associated with clinical outcomes;
- The discovery that ETS fusion genes, the most common mutation in prostate tumours, perturb the proteome and transcriptome in dramatically divergent ways, particularly influencing metabolic pathways;
- The discovery that RNA abundance explains only ~10% of variability in protein levels in prostate cancer, but there is a broad network of trans effects that converge on specific functional pathways; and
- The discovery that biomarkers comprising genomic and proteomic features significantly out-perform those comprised of either molecular feature alone.
Once validated, this resource may be able to help improve treatments for patients with localized prostate cancer by providing doctors and researchers with more precise biomarkers to stratify patients more effectively. This, in turn, may help them tailor treatments to match the specific needs of their patients, as determined by their complete proteogenomic profile.
“Our data suggests that profiling a tumour tissue at multiple levels improves biomarker performance,” said Dr. Kislinger, medical biophysics chair at the University of Toronto and co-principal investigator on several TFRI-funded projects. “Application of this concept to non-invasive biomarker development, for example in urine, and integration with rapidly improving imaging approaches, could provide significant improvements to patient management, for example for men on active surveillance, sparing them unnecessary needle biopsies while providing more informed treatment options.”
The Proteogenomic Landscape of Curable Prostate Cancer
Ankit Sinha, Vincent Huang, Julie Livingstone, Jenny Wang, Natalie S. Fox, Natalie Kurganovs, Vladimir Ignatchenko, Katharina Fritsch, Nilgun Donmez, Lawrence E. Heisler, Yu-Jia Shiah, Cindy Q. Yao, Javier A. Alfaro, Stas Volik, Anna Lapuk, Michael Fraser, Ken Kron, Alex Murison, Mathieu Lupien, Cenk Sahinalp, Colin C. Collins, Bernard Tetu, Mehdi Masoomian, David M. Berman, Theodorus van der Kwast, Robert G. Bristow, Thomas Kislinger, and Paul C. Boutros
This study is partially funded by a Terry Fox New Investigator Award in Systems Biology of Tumour Hypoxia to Dr. Paul Boutros