TY - JOUR
T1 - Novel biomarker signature that may predict aggressive disease in African American men with prostate cancer
AU - Yamoah, Kosj
AU - Johnson, Michael H.
AU - Choeurng, Voleak
AU - Faisal, Farzana A.
AU - Yousefi, Kasra
AU - Haddad, Zaid
AU - Ross, Ashley E.
AU - Alshalafa, Mohammed
AU - Den, Robert
AU - Lal, Priti
AU - Feldman, Michael
AU - Dicker, Adam P.
AU - Klein, Eric A.
AU - Davicioni, Elai
AU - Rebbeck, Timothy R.
AU - Schaeffer, Edward M.
N1 - Publisher Copyright:
© 2015 by American Society of Clinical Oncology.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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 medica centers were matched according to the Cancer of the Prostate Risk Assessment postsurgica 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.
AB - 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 medica centers were matched according to the Cancer of the Prostate Risk Assessment postsurgica 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.
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U2 - 10.1200/JCO.2014.59.8912
DO - 10.1200/JCO.2014.59.8912
M3 - Article
C2 - 26195723
AN - SCOPUS:84941354031
SN - 0732-183X
VL - 33
SP - 2789
EP - 2796
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 25
ER -