Epigenetic Test Might Be Prognostic in Prostate Cancer

Roxanne Nelson

February 04, 2014

SAN FRANCISCO — Epigenetic profiling of certain genes might have prognostic value and could help identify patients with aggressive types of prostate cancer, according to a pilot study.

The researchers found a positive correlation between Gleason score and the methylation levels of all genes examined. Levels were significantly lower in patients with a lower risk profile, and higher in those more likely to have an adverse prognosis.

"The correlation isn't perfect, but there is a correlation," said lead researcher Leander Van Neste, PhD, from Maastricht University in the Netherlands and MDxHealth, the company developing the test. "All of these genes we profiled already have a decent body of evidence suggesting that methylation has some prognostic affect."

The study results were presented here at the 2014 Genitourinary Cancers Symposium.

Dr. Van Neste pointed out that the samples used in this study were obtained from patients who had undergone a radical prostatectomy. "These patients had already been treated, but the test could have significant clinical applications if it is done with biopsied tissue instead," he told Medscape Medical News.

"This is just a pilot study. We need to run a study with biopsy tissue to get the larger picture and evaluate the full utility of this test," Dr. Van Neste explained. "If what we are displaying here can be applied to biopsied tissue, we may be able to see who is a candidate for watchful waiting and who needs more aggressive therapy. That is the ultimate use we are hoping for."

Study Details

Dr. Van Neste and colleagues obtained 84 samples from patients who had undergone prostatectomy and who had Gleason scores of 6 (n = 6), 3+4 (n = 41), 4+3 (n = 26), and at least 8 (n = 11). Methylation-specific polymerase chain reaction was used to epigenetically profile the samples for GSTP1, APC, RASSF1, RARB, and GAL3 methylation.

The researchers used Ward's method to perform unsupervised hierarchical clustering and examine the association between DNA methylation patterns and Gleason scores. Methylation ratios were scaled across all samples by calculating a Z-score for each gene.

The hierarchical clustering analyses resulted in 3 distinct clusters. One cluster had a general depletion of methylation; a second cluster had high methylation levels in most genes, particularly RARB; and a third cluster exhibited intermediate methylation signals and fewer concurrently methylated genes.

Of note, the methylation levels of all 5 genes were significantly lower in samples with Gleason scores of 3+4 or less than in those with Gleason scores of 4+3 or higher (P  < .05 for all).

Low methylation signals were associated with 100% of samples with a Gleason score of 6 and 80% of samples with a Gleason score of 3+4. Intermediate or high methylation levels were associated with 81% of samples with a Gleason score of 4+3 and 82% of samples with a Gleason score of at least 8.

In this cohort, the test was useful for upgrading disease, Dr. Van Neste noted. The research team is currently collecting biopsy samples to further evaluate this test.

MDxHealth has recently developed another test that is now commercially available, as previously reported by Medscape Medical News. The ConfirmMDx for Prostate Cancer uses an epigenetic assay consisting of 3 biomarkers to help urologists distinguish patients who have a true negative biopsy from those at risk for occult cancer.

All of the authors report employment, stock ownership, or other association with MDxHealth, which is developing the test.

2014 Genitourinary Cancers Symposium (GUCS). Abstract 197. Presented January 31, 2014.

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