title: Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. Kosj.Yamoah@moffitt.org.
authors.forename: Kosj
authors.initials: K
authors.lastname: Yamoah
authors.affiliation: 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.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Johnson
authors.affiliation: 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.
authors.forename: Voleak
authors.initials: V
authors.lastname: Choeurng
authors.affiliation: 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.
authors.forename: Farzana A
authors.initials: FA
authors.lastname: Faisal
authors.affiliation: 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.
authors.forename: Kasra
authors.initials: K
authors.lastname: Yousefi
authors.affiliation: 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.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Haddad
authors.affiliation: 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.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Ross
authors.affiliation: 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.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alshalafa
authors.affiliation: 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.
authors.forename: Robert
authors.initials: R
authors.lastname: Den
authors.affiliation: 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.
authors.forename: Priti
authors.initials: P
authors.lastname: Lal
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Feldman
authors.affiliation: 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.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
authors.affiliation: 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.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.affiliation: 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.
authors.forename: Elai
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: 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.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.affiliation: 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.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schaeffer
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics / Q000473:pathology*; D019998:Racemases and Epimerases / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C072312:ERG protein, human; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; C410824:GOLM1 protein, human; D018398:Homeodomain Proteins; D008565:Membrane Proteins; C491178:NKX3-1 protein, human; D011944:Receptors, Androgen; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; C486642:SPINK1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase