Fatal Prostate Cancer Differentiated from Manageable Cancer

Human prostate cancers display numerous DNA methylation changes compared to normal tissue samples. However, definitive identification of features related to the cells’ malignant status has been compromised by the predominance of cells with luminal features in prostate cancers.

A recent study showed that more than 25 men were being unnecessarily treated with surgery or radiotherapy, for every single life saved. It is believed that success rates could be hindered as a result of treating all prostate cancers in the same way. A test has been designed that can pick out life-threatening prostate cancers, with up to 92% accuracy.

Scientists at the University of York (York, UK) and the University of British Columbia (Vancouver, BC, Canada) generated genome-wide DNA methylation profiles of cell subpopulations with basal or luminal features isolated from matched prostate cancer and normal tissue samples. The team analyzed more than 500 cancer tissue samples and compared them with non-cancer tissue to search for patterns of a chemical group that is added to part of the DNA molecule, altering gene expression.

The team reported that many frequent DNA methylation changes previously attributed to prostate cancers were identified as differences between luminal and basal cells in both normal and cancer samples. They also identified changes unique to each of the two cancer subpopulations. Those specific to cancer luminal cells were associated with regulation of metabolic processes, cell proliferation and epithelial development.

Within the prostate cancer TCGA dataset, these changes were able to distinguish not only cancers from normal samples, but also organ-confined cancers from those with extraprostatic extensions. Using changes present in both basal and luminal cancer cells, they derived a new 17-CpG prostate cancer signature with high predictive power in the TCGA dataset.

Davide Pellacani, PhD, the lead senior author of the study, said, “Using this computer analysis, not only could we see which tissue samples had cancer and which didn't, but also which cancers were dangerous and which ones less so. Out of almost a million markers studied, we were able to use our new tools to single out differences in cancer potency.” The study was published on October 15, 2018, in the journal British Journal of Cancer.

Related Links:
University of York
University of British Columbia