African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome

Michelle I. Echevarria, Shivanshu Awasthi, Chia Ho Cheng, Anders E. Berglund, Robert J. Rounbehler, Travis A. Gerke, Mandeep Takhar, Elai Davicioni, Eric A. Klein, Stephen J. Freedland, Ashley E. Ross, Edward M. Schaeffer, Robert B. Den, John L. Cleveland, Jong Y. Park, Walter Rayford, Kosj Yamoah

Research output: Contribution to journalArticle

Abstract

Purpose:Most prostate cancer in African American men lacks the ETS (E26 transforming specific) family fusion event (ETS-). We aimed to establish clinically relevant biomarkers in African American men by studying ETS dependent gene expression patterns to identified race specific genes predictive of outcomes.Materials and Methods:Two multicenter cohorts of a total of 1,427 men were used for the discovery and validation (635 and 792 men, respectively) of race specific predictive biomarkers. We used false discovery rate adjusted q values to identify race and ETS dependent genes which were differentially expressed in African American men who experienced biochemical recurrence within 5 years. Principal component modeling along with survival analysis was done to assess the accuracy of the gene panel in predicting recurrence.Results:We identified 3,047 genes which were differentially expressed based on ETS status. Of these genes 362 were differentially expressed in a race specific manner (false discovery rate 0.025 or less). A total of 81 genes were race specific and over expressed in African American men who experienced biochemical recurrence. The final gene panel included APOD, BCL6, EMP1, MYADM, SRGN and TIMP3. These genes were associated with 5-year biochemical recurrence (HR 1.97, 95%CI 1.27-3.06, p=0.002) and they improved the predictive accuracy of clinicopathological variables only in African American men (60-month time dependent AUC 0.72).Conclusions:In an effort to elucidate biological features associated with prostate cancer aggressiveness in African American men we identified ETS dependent biomarkers predicting early onset biochemical recurrence only in African American men. Thus, these ETS dependent biomarkers representing ideal candidates for biomarkers of aggressive disease in this patient population.

Original languageEnglish (US)
Pages (from-to)247-255
Number of pages9
JournalJournal of Urology
Volume202
Issue number2
DOIs
StatePublished - Aug 1 2019

Fingerprint

African Americans
Prostatic Neoplasms
Genes
Biomarkers
Recurrence
Survival Analysis
Area Under Curve
Gene Expression
Population

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Echevarria, M. I., Awasthi, S., Cheng, C. H., Berglund, A. E., Rounbehler, R. J., Gerke, T. A., ... Yamoah, K. (2019). African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome. Journal of Urology, 202(2), 247-255. https://doi.org/10.1097/JU.0000000000000193

African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome. / Echevarria, Michelle I.; Awasthi, Shivanshu; Cheng, Chia Ho; Berglund, Anders E.; Rounbehler, Robert J.; Gerke, Travis A.; Takhar, Mandeep; Davicioni, Elai; Klein, Eric A.; Freedland, Stephen J.; Ross, Ashley E.; Schaeffer, Edward M.; Den, Robert B.; Cleveland, John L.; Park, Jong Y.; Rayford, Walter; Yamoah, Kosj.

In: Journal of Urology, Vol. 202, No. 2, 01.08.2019, p. 247-255.

Research output: Contribution to journalArticle

Echevarria, MI, Awasthi, S, Cheng, CH, Berglund, AE, Rounbehler, RJ, Gerke, TA, Takhar, M, Davicioni, E, Klein, EA, Freedland, SJ, Ross, AE, Schaeffer, EM, Den, RB, Cleveland, JL, Park, JY, Rayford, W & Yamoah, K 2019, 'African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome', Journal of Urology, vol. 202, no. 2, pp. 247-255. https://doi.org/10.1097/JU.0000000000000193
Echevarria MI, Awasthi S, Cheng CH, Berglund AE, Rounbehler RJ, Gerke TA et al. African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome. Journal of Urology. 2019 Aug 1;202(2):247-255. https://doi.org/10.1097/JU.0000000000000193
Echevarria, Michelle I. ; Awasthi, Shivanshu ; Cheng, Chia Ho ; Berglund, Anders E. ; Rounbehler, Robert J. ; Gerke, Travis A. ; Takhar, Mandeep ; Davicioni, Elai ; Klein, Eric A. ; Freedland, Stephen J. ; Ross, Ashley E. ; Schaeffer, Edward M. ; Den, Robert B. ; Cleveland, John L. ; Park, Jong Y. ; Rayford, Walter ; Yamoah, Kosj. / African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome. In: Journal of Urology. 2019 ; Vol. 202, No. 2. pp. 247-255.
@article{e64e44ff805445209960baf887060813,
title = "African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome",
abstract = "Purpose:Most prostate cancer in African American men lacks the ETS (E26 transforming specific) family fusion event (ETS-). We aimed to establish clinically relevant biomarkers in African American men by studying ETS dependent gene expression patterns to identified race specific genes predictive of outcomes.Materials and Methods:Two multicenter cohorts of a total of 1,427 men were used for the discovery and validation (635 and 792 men, respectively) of race specific predictive biomarkers. We used false discovery rate adjusted q values to identify race and ETS dependent genes which were differentially expressed in African American men who experienced biochemical recurrence within 5 years. Principal component modeling along with survival analysis was done to assess the accuracy of the gene panel in predicting recurrence.Results:We identified 3,047 genes which were differentially expressed based on ETS status. Of these genes 362 were differentially expressed in a race specific manner (false discovery rate 0.025 or less). A total of 81 genes were race specific and over expressed in African American men who experienced biochemical recurrence. The final gene panel included APOD, BCL6, EMP1, MYADM, SRGN and TIMP3. These genes were associated with 5-year biochemical recurrence (HR 1.97, 95{\%}CI 1.27-3.06, p=0.002) and they improved the predictive accuracy of clinicopathological variables only in African American men (60-month time dependent AUC 0.72).Conclusions:In an effort to elucidate biological features associated with prostate cancer aggressiveness in African American men we identified ETS dependent biomarkers predicting early onset biochemical recurrence only in African American men. Thus, these ETS dependent biomarkers representing ideal candidates for biomarkers of aggressive disease in this patient population.",
author = "Echevarria, {Michelle I.} and Shivanshu Awasthi and Cheng, {Chia Ho} and Berglund, {Anders E.} and Rounbehler, {Robert J.} and Gerke, {Travis A.} and Mandeep Takhar and Elai Davicioni and Klein, {Eric A.} and Freedland, {Stephen J.} and Ross, {Ashley E.} and Schaeffer, {Edward M.} and Den, {Robert B.} and Cleveland, {John L.} and Park, {Jong Y.} and Walter Rayford and Kosj Yamoah",
year = "2019",
month = "8",
day = "1",
doi = "10.1097/JU.0000000000000193",
language = "English (US)",
volume = "202",
pages = "247--255",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome

AU - Echevarria, Michelle I.

AU - Awasthi, Shivanshu

AU - Cheng, Chia Ho

AU - Berglund, Anders E.

AU - Rounbehler, Robert J.

AU - Gerke, Travis A.

AU - Takhar, Mandeep

AU - Davicioni, Elai

AU - Klein, Eric A.

AU - Freedland, Stephen J.

AU - Ross, Ashley E.

AU - Schaeffer, Edward M.

AU - Den, Robert B.

AU - Cleveland, John L.

AU - Park, Jong Y.

AU - Rayford, Walter

AU - Yamoah, Kosj

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Purpose:Most prostate cancer in African American men lacks the ETS (E26 transforming specific) family fusion event (ETS-). We aimed to establish clinically relevant biomarkers in African American men by studying ETS dependent gene expression patterns to identified race specific genes predictive of outcomes.Materials and Methods:Two multicenter cohorts of a total of 1,427 men were used for the discovery and validation (635 and 792 men, respectively) of race specific predictive biomarkers. We used false discovery rate adjusted q values to identify race and ETS dependent genes which were differentially expressed in African American men who experienced biochemical recurrence within 5 years. Principal component modeling along with survival analysis was done to assess the accuracy of the gene panel in predicting recurrence.Results:We identified 3,047 genes which were differentially expressed based on ETS status. Of these genes 362 were differentially expressed in a race specific manner (false discovery rate 0.025 or less). A total of 81 genes were race specific and over expressed in African American men who experienced biochemical recurrence. The final gene panel included APOD, BCL6, EMP1, MYADM, SRGN and TIMP3. These genes were associated with 5-year biochemical recurrence (HR 1.97, 95%CI 1.27-3.06, p=0.002) and they improved the predictive accuracy of clinicopathological variables only in African American men (60-month time dependent AUC 0.72).Conclusions:In an effort to elucidate biological features associated with prostate cancer aggressiveness in African American men we identified ETS dependent biomarkers predicting early onset biochemical recurrence only in African American men. Thus, these ETS dependent biomarkers representing ideal candidates for biomarkers of aggressive disease in this patient population.

AB - Purpose:Most prostate cancer in African American men lacks the ETS (E26 transforming specific) family fusion event (ETS-). We aimed to establish clinically relevant biomarkers in African American men by studying ETS dependent gene expression patterns to identified race specific genes predictive of outcomes.Materials and Methods:Two multicenter cohorts of a total of 1,427 men were used for the discovery and validation (635 and 792 men, respectively) of race specific predictive biomarkers. We used false discovery rate adjusted q values to identify race and ETS dependent genes which were differentially expressed in African American men who experienced biochemical recurrence within 5 years. Principal component modeling along with survival analysis was done to assess the accuracy of the gene panel in predicting recurrence.Results:We identified 3,047 genes which were differentially expressed based on ETS status. Of these genes 362 were differentially expressed in a race specific manner (false discovery rate 0.025 or less). A total of 81 genes were race specific and over expressed in African American men who experienced biochemical recurrence. The final gene panel included APOD, BCL6, EMP1, MYADM, SRGN and TIMP3. These genes were associated with 5-year biochemical recurrence (HR 1.97, 95%CI 1.27-3.06, p=0.002) and they improved the predictive accuracy of clinicopathological variables only in African American men (60-month time dependent AUC 0.72).Conclusions:In an effort to elucidate biological features associated with prostate cancer aggressiveness in African American men we identified ETS dependent biomarkers predicting early onset biochemical recurrence only in African American men. Thus, these ETS dependent biomarkers representing ideal candidates for biomarkers of aggressive disease in this patient population.

UR - http://www.scopus.com/inward/record.url?scp=85069297190&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069297190&partnerID=8YFLogxK

U2 - 10.1097/JU.0000000000000193

DO - 10.1097/JU.0000000000000193

M3 - Article

VL - 202

SP - 247

EP - 255

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 2

ER -