Biomarkers offer insight into PCa racial disparity

A newly identified subset of prostate cancer biomarkers could help explain why African-American men are more likely than European-American men to develop and die from prostate cancer.

As reported online in the Journal of Clinical Oncology (July 20, 2015), the Decipher test platform identified a subset of genes that define a genomic prostate cancer subtype that is more common in African-American men and indicates more aggressive disease. The study was conducted by U.S. and Canadian researchers, including those from Thomas Jefferson University, Philadelphia.

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The authors examined 20 biomarkers associated with the cancer’s initiation and progression and compared findings between 154 African-American and 243 European-American patient samples pulled from the Decipher Genomics Resource Information Database, according to a press release from GenomeDx Biosciences, which makes the Decipher test. Researchers matched the patients’ prostate cancer characteristics using the CAPRA-S validated scoring system and then studied patients’ samples to determine which of the 20 genes were expressed in high or low quantities in the two groups.

Six of the 20 biomarkers showed statistically significant differential expression in African-American men: ERG, AMACR, SPINK1, NKX3-1, GOLM1, and androgen receptor. Dysregulation of AMACR, ERG, FOXP1, and GSTP1, along with loss-of-function mutations for tumor suppressors NKX3-1 and RB1, predicted risk of pathologic T3 disease in an ethnicity-dependent manner. And dysregulation of GOLM1, SRD5A2, and MKi67 predicted 3-year biochemical recurrence and metastasis at 5 years, according to the study’s abstract.

NEXT: 'Triple negative prostate cancer' subtype

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The authors uncovered what they called a “triple negative prostate cancer” subtype, defined as low or no levels of the genes ERG, ETX, and SPINK1. Fifty-one percent of the African-Americans in the study had triple negative disease versus 35% of European-Americans.

African-American men with high CAPRA-S scores and more advanced Gleason grade disease at diagnosis were more likely to be triple negative when compared to European-American men with a similar disease score at diagnosis. The authors also found other genes that were expressed at different levels in African-American versus European-American men, including genes involved in cell metabolism and the androgen receptor pathway, according to a Thomas Jefferson University press release.

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While this is the largest study on African-American prostate cancer biomarkers, the number of African-American patients studied is relatively small.

The study suggests that a subset of African-American men may have a type of prostate cancer that comes from molecular pathways that are different from those of European-American men, according to first author Kosj Yamoah, MD, PhD, a Thomas Jefferson resident at the time of the study who is currently at Moffitt Cancer Center and Research Institute, Tampa, FL.

“This, and our previous work in this area, shows that some African-American men with prostate cancer might have a better shot at survival if they are treated with a different approach than standard of care,” Dr. Yamoah said.

NEXT - Dr. Gomella: Information could help identify diagnostic, treatment strategies

The disparity in the presentation and outcomes of African-Americans with prostate cancer has been a concern for years with few answers, according to Leonard G. Gomella, MD, of Thomas Jefferson University’s Sidney Kimmel Cancer Center.

“Armed with this new genomic information, including the unique ‘triple negative’ prostate cancer signature, will allow us to identify diagnostic and treatment strategies to address this important clinical challenge,” said Dr. Gomella, who was not an author on the study.

The next steps, according to Dr. Yamoah, are to refine the biomarkers that will capture these differences and develop approaches to help reduce outcome disparities.

One study co-author is an employee of GenomeDx Biosciences.