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African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome

2019; Lippincott Williams & Wilkins; Volume: 202; Issue: 2 Linguagem: Inglês

10.1097/ju.0000000000000193

1527-3792

M. Echevarria, Shivanshu Awasthi, Chia‐Ho Cheng, Anders Berglund, Robert J. Rounbehler, Travis 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,

Glutathione Transferases and Polymorphisms

No AccessJournal of UrologyAdult Urology1 Aug 2019African American Specific Gene Panel Predictive of Poor Prostate Cancer OutcomeThis article is commented on by the following:Editorial CommentEditorial Comment 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, and Kosj Yamoah Michelle I. EchevarriaMichelle I. Echevarria H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida , Shivanshu AwasthiShivanshu Awasthi H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida , Chia-Ho ChengChia-Ho Cheng H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida , Anders E. BerglundAnders E. Berglund H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida , Robert J. RounbehlerRobert J. Rounbehler H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida , Travis A. GerkeTravis A. Gerke H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida , Mandeep TakharMandeep Takhar GenomeDx Biosciences, Vancouver, British Columbia, Canada , Elai DavicioniElai Davicioni GenomeDx Biosciences, Vancouver, British Columbia, Canada , Eric A. KleinEric A. Klein Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio , Stephen J. FreedlandStephen J. Freedland Cedars-Sinai, Los Angeles, California , Ashley E. RossAshley E. Ross Johns Hopkins University, Baltimore, Maryland , Edward M. SchaefferEdward M. Schaeffer Northwestern University, Evanston, Illinois , Robert B. DenRobert B. Den Sidney Kimmel Medical College at Thomas Jefferson University, Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania , John L. ClevelandJohn L. Cleveland H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida , Jong Y. ParkJong Y. Park H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida , Walter RayfordWalter Rayford The Urology Group, P. C., Memphis, Tennessee , and Kosj YamoahKosj Yamoah ‡Correspondence: 12902 Magnolia Dr., Tampa, Florida 33612 telephone: 813-745-3053; FAX: 813-745-7231; E-mail Address: [email protected] H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida View All Author Informationhttps://doi.org/10.1097/JU.0000000000000193AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail 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. References 1. : Cancer statistics, 2017. CA Cancer J Clin 2017; 67: 7. Google Scholar 2. : SEER Cancer Statistics Review. Available at http://seer.cancer.gov/csr/1975_2007/. Accessed September 18, 2017. Google Scholar 3. : African-American men and prostate cancer-specific mortality: a competing risk analysis of a large institutional cohort, 1989-2015. Cancer Med 2018; 7: 2160. 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No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. © 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byCullen J, Lynch J, Klein E, Van Den Eeden S, Carroll P, Mohler J, Knezevic D, Farrington T and Lu R (2020) Multicenter Comparison of 17-Gene Genomic Prostate Score as a Predictor of Outcomes in African American and Caucasian American Men with Clinically Localized Prostate CancerJournal of Urology, VOL. 205, NO. 4, (1047-1054), Online publication date: 1-Apr-2021.Smith J (2019) This Month in Adult UrologyJournal of Urology, VOL. 202, NO. 2, (181-182), Online publication date: 1-Aug-2019.Related articlesJournal of Urology8 Jul 2019Editorial CommentJournal of Urology8 Jul 2019Editorial Comment Volume 202Issue 2August 2019Page: 247-255Supplementary Materials Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.Keywordsneoplasm recurrenceneoplastictumorgene expression regulationAfrican Americansbiomarkerslocalprostatic neoplasmsMetricsAuthor Information Michelle I. Echevarria H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida Equal study contribution. More articles by this author Shivanshu Awasthi H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida Equal study contribution. More articles by this author Chia-Ho Cheng H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida More articles by this author Anders E. Berglund H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida More articles by this author Robert J. Rounbehler H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida More articles by this author Travis A. Gerke H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida More articles by this author Mandeep Takhar GenomeDx Biosciences, Vancouver, British Columbia, Canada More articles by this author Elai Davicioni GenomeDx Biosciences, Vancouver, British Columbia, Canada More articles by this author Eric A. Klein Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio More articles by this author Stephen J. Freedland Cedars-Sinai, Los Angeles, California More articles by this author Ashley E. Ross Johns Hopkins University, Baltimore, Maryland Financial interest and/or other relationship with Genome Dx Biosciences. More articles by this author Edward M. Schaeffer Northwestern University, Evanston, Illinois More articles by this author Robert B. Den Sidney Kimmel Medical College at Thomas Jefferson University, Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania More articles by this author John L. Cleveland H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida More articles by this author Jong Y. Park H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida More articles by this author Walter Rayford The Urology Group, P. C., Memphis, Tennessee More articles by this author Kosj Yamoah H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida ‡Correspondence: 12902 Magnolia Dr., Tampa, Florida 33612 telephone: 813-745-3053; FAX: 813-745-7231; E-mail Address: [email protected] More articles by this author Expand All The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. Supported by the Prostate Cancer Foundation Young Investigator Award (KY), American Cancer Society Grant MRSG-17-108-01-TBG (KY), the V Foundation (KY, JYP) and the NCI Comprehensive Cancer Center P30 CA076292 Grant (Moffitt Cancer Center). 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