Biomarker Signature May Predict Aggressive Disease in African American Men With Prostate Cancer
- Dysregulation of AMACR, ERG, FOXP1, and GSTP1 and loss-of-function mutations for tumor suppressors NKX3-1 and RB1 were associated with a significantly increased risk of pathologic T3 disease in African American men.
- Dysregulation of GOLM1 was associated with an increased risk of 3-year biochemical recurrence in African American men.
In a study reported in Journal of Clinical Oncology, Yamoah et al identified a biomarker signature that may predict aggressive disease in African American men with prostate cancer.
In the study, distribution of mRNA expression levels of 20 biomarkers associated with prostate cancer initiation and progression were compared in 154 African American and 243 European American patients matched for Cancer of the Prostate Risk Assessment postsurgical score using false discovery rate, adjusted Wilcoxon-Mann-Whitney, and logistic regression models.
Six biomarkers showed significant differential expression in African American vs European American men in at least one statistical model: ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1 (P =.03), GOLM1 (P = .03), and androgen receptor (P = .04). A greater proportion of African American men were negative for variants in ERG, ETS, and SPINK1 (“triple-negative”; 51% vs 35%, P = .002).
Dysregulation of AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), and GSTP1 (P = .049) and loss-of-function mutations for tumor suppressors NKX3-1 (P = .025) and RB1 (P = .037) were associated with significantly increased risk of pathologic T3 disease in African American men and had a significant ethnicity-by-biomarker interaction.
Dysregulation of GOLM1 (P = .037) was associated with increased risk of 3-year biochemical recurrence in African American men. Dysregulation of SRDA2 (P = .013) and MKi67 (P = .023) was associated with increased risk of 3-year biochemical recurrence, and dysregulation of SRD5A2 (P = .023) was associated with increased risk of metastatic disease at 5 years in an ethnicity-independent manner.
The investigators concluded: “We have identified a subset of [prostate cancer] biomarkers that predict the risk of clinicopathologic outcomes in an ethnicity-dependent manner. These biomarkers may explain in part the biologic contribution to ethnic disparity in [prostate cancer] outcomes between [European American] and [African American] men.”
Kosj Yamoah, MD, PhD, of Moffitt Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
The study was funded by the U.S. Department of Defense, Prostate Cancer Foundation, and Public Health Service grants/awards. For full disclosures of the study authors, visit jco.ascopubs.org.