We identify and validate accurate diagnostic biomarkers for prostate cancer through a systematic evaluation of DNA methylation alterations.

We assembled three early prostate cancer cohorts (total patients = 699) from which we collected and processed over 1300 prostatectomy tissue samples for DNA extraction. Using real-time methylation-specific PCR, we measured normalized methylation levels at 15 frequently methylated loci. After partitioning sample sets into independent training and validation cohorts, classifiers were developed using logistic regression, analyzed, and validated.

In the training dataset, DNA methylation levels at 7 of 15 genomic loci (glutathione S-transferase Pi 1 [GSTP1], CCDC181, hyaluronan, and proteoglycan link protein 3 [HAPLN3], GSTM2, growth arrest-specific 6 [GAS6], RASSF1, and APC) showed large differences between cancer and benign samples. The best binary classifier was the GAS6/GSTP1/HAPLN3 logistic regression model, with an area under these curves of 0.97, which showed a sensitivity of 94%, and a specificity of 93% after external validation.

We created and validated a multigene model for the classification of benign and malignant prostate tissue. With false positive and negative rates below 7%, this three-gene biomarker represents a promising basis for more accurate prostate cancer diagnosis.

The Prostate. 2019 Aug 21 [Epub ahead of print]

Palak G Patel, Thomas Wessel, Atsunari Kawashima, John B A Okello, Tamara Jamaspishvili, Karl-Philippe Guérard, Laura Lee, Anna Ying-Wah Lee, Nathan E How, Dan Dion, Eleonora Scarlata, Chelsea L Jackson, Suzanne Boursalie, Tanya Sack, Rachel Dunn, Madeleine Moussa, Karen Mackie/, Audrey Ellis, Elizabeth Marra, Joseph Chin, Khurram Siddiqui, Khalil Hetou, Lee-Anne Pickard, Vinolia Arthur-Hayward, Glenn Bauman, Simone Chevalier, Fadi Brimo, Paul C Boutros, Jacques Lapointe PhD, John M S Bartlett, Robert J Gooding, David M Berman

Department of Pathology & Molecular Medicine, Queen’s University, Kingston, Ontario, Canada., Life Sciences Group, Thermo Fisher Scientific, Waltham, Massachusetts., Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, Québec, Canada., Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada., Division of Surgical Pathology, Departmant of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada., Department of Surgery (Urology), London Health Sciences Centre, London, ON, Canada., Ontario Tumor Bank, Toronto, Ontario, Canada., Division of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada., Department of Pathology, McGill University Health Center and McGill University, Montreal, Québec, Canada., Diagnostic Development, Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada., Division of Cancer Biology & Genetics, Queen’s Cancer Research Institute, Queen’s University, Kingston, Ontario, Canada.