MP07-16 DEVELOPMENT OF PROSTATE CANCER GENE SIGNATURES AND GENE SCORES OF AGGRESSIVENESS FOR AFRICAN AMERICANS AND EUROPEANS AMERICANS

Abstract

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 2016MP07-16 DEVELOPMENT OF PROSTATE CANCER GENE SIGNATURES AND GENE SCORES OF AGGRESSIVENESS FOR AFRICAN AMERICANS AND EUROPEANS AMERICANS Isaac Powell, Greg Dyson, and Aliccia Bollig-Fischer Isaac PowellIsaac Powell More articles by this author , Greg DysonGreg Dyson More articles by this author , and Aliccia Bollig-FischerAliccia Bollig-Fischer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2219AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There is considerable clinical and biological PCa heterogeneity that sometimes creates clinical indecision in determining aggressive vs non-aggressive PCa. It is clear based on our reported analysis that prostate cancer (PCa) functional and driver genes are significantly and differentially expressed among African American men (AAM) compared to European American men (EAM). (Powell 2013) We are developing gene panels for AAM and EAM to establish gene signatures and gene scores per patient that may improve the precision of PCa diagnosis of aggressive vs non-aggressive disease. We present these results as proof of principle. METHODS To derive a gene signature and score, we examined 21 genes identified among those that showed significant differential expression comparing AAM and EAM according to results from our earlier publication cited above. Utilizing an aggressiveness phenotype (aggressive PCa defined as GS=8 or 7 (4+3), T3 disease and BCR within 3 years; non-aggressive PCa includes GS = 6, T2 disease, and no BCR within 5 years), we identified the optimal threshold for each gene individually by race in predicting disease aggressiveness using recursive partitioning (requiring at least 30% of the sample to be in both of the daughter nodes). This resulted in a high-risk and a low-risk subset for each gene for each race. Subsequently, the number of genes that a patient has that are high risk are summed to create a gene score. Recursive partitioning is again used to define a threshold for the gene score for each race. RESULTS The resultant sensitivity and specificity for AAM with 11 or more high risk genes is 100% and 69%, respectively. The resultant sensitivity and specificity for EAM with 10 or more high risk genes is 88% and 85%, respectively. The corresponding ROC curves illustrate that even with a small number of genes, we can create a reasonably good classifier for disease aggressiveness. We have developed gene scores for AAM and EAM based on our results of microarray gene expression analysis as high risk, described in the methods, as predicting aggressiveness. Race-specific thresholds for prostate cancer aggressiveness were determined as follows: if an AAM patient had at least 11 of 21 genes that were high-risk or an EAM patient had at least 10 of 21 genes that were high-risk. (Genes to be presented). CONCLUSIONS This is proof of principle that we can develop race-specific prostate cancer gene signatures and scores of aggressiveness that may be useful to improve our ability to accurately predict disease advancement. Future plans include an investigation of the utility of next generation sequencing to expand and improve our current biomarker development. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e83 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Isaac Powell More articles by this author Greg Dyson More articles by this author Aliccia Bollig-Fischer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...