Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer.

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
• Edward M Schaeffer

Publication/Presentation Date

9-1-2015

Abstract

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.

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.

Volume

33

Issue

25

First Page

2789

Last Page

2796

ISSN

1527-7755

Published In/Presented At

Yamoah, K., Johnson, M. H., Choeurng, V., Faisal, F. A., Yousefi, K., Haddad, Z., Ross, A. E., Alshalafa, M., Den, R., Lal, P., Feldman, M., Dicker, A. P., Klein, E. A., Davicioni, E., Rebbeck, T. R., & Schaeffer, E. M. (2015). Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 33(25), 2789–2796. https://doi.org/10.1200/JCO.2014.59.8912

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

26195723

Department(s)

Administration and Leadership

Document Type

Article