Purpose: We studied the ethnicity-specific expression of prostate cancer (PC) –associated biomarkers to evaluate whether genetic/biologic factors affect ethnic disparities in PC pathogenesis and disease progression.
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Patients and Methods: A total of 154 African American (AA) and 243 European American (EA) patients from four medical centers were matched according to the Cancer of the Prostate Risk Assessment postsurgical score within each institution. The distribution of mRNA expression levels of 20 validated biomarkers reported to be associated with PC initiation and progression was compared with ethnicity using false discovery rate, adjusted Wilcoxon-Mann-Whitney, and logistic regression models. A conditional logistic regression model was used to evaluate the interaction between ethnicity and biomarkers for predicting clinicopathologic outcomes.
Results: Of the 20 biomarkers examined, six showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1 (P = .03), GOLM1 (P = .03), and androgen receptor (P = .04). Dysregulation of AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), and GSTP1 (P = .049) as well as loss-of-function mutations for tumor suppressors NKX3-1 (P = .025) and RB1 (P = .037) predicted risk of pathologic T3 disease in an ethnicity-dependent manner. Dysregulation of GOLM1 (P = .037), SRD5A2 (P = .023), and MKi67 (P = .023) predicted clinical outcomes, including 3-year biochemical recurrence and metastasis at 5 years. A greater proportion of AA men than EA men had triple-negative (ERG-negative/ETS-negative/SPINK1-negative) disease (51% v 35%; P = .002).
Conclusion: We have identified a subset of PC 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 PC outcomes between EA and AA men.
Both K.Y. and M.H.J. as first authors, and both T.R.R. and E.M.S. as senior authors, contributed equally to this work.
This work was funded in part by US Department of Defense Grant No. PC-121189, by the Prostate Cancer Foundation Young Investigator award (to K.Y.), and by Public Health Service Grant No. P60-MD006900 (to T.R.R.).
Published online before printJuly 20, 2015, doi:10.1200/JCO.2014.59.8912 JCO July 20, 2015JCO.2014.59.8912 .
Authors: Kosj Yamoah⇑, Michael H. Johnson, Voleak Choeurng, Farzana A. Faisal, Kasra Yousefi, Zaid Haddad, Ashley E. Ross, Mohammed Alshalafa, Robert Den, Priti Lal, Michael Feldman, Adam P. Dicker, Eric A. Klein, Elai Davicioni, Timothy R. Rebbeck and Edward M. Schaeffer
Affiliations: Kosj Yamoah, Robert Den, and Adam P. Dicker, Thomas Jefferson University Hospital; Priti Lal, Michael Feldman, and Timothy R. Rebbeck, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kosj Yamoah, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Michael H. Johnson, Farzana A. Faisal, Ashley E. Ross, and Edward M. Schaeffer, Johns Hopkins University, Baltimore, MD; Voleak Choeurng, Kasra Yousefi, Zaid Haddad, Mohammed Alshalafa, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada; and Eric A. Klein, The Cleveland Clinic Foundation, Cleveland, OH.