Abstract 4280: Genome-wide expression and methylation analysis in CD31+ cells from African American and Caucasian American benign and malignant prostate tissue

Abstract

Abstract Prostate cancer exhibits striking racial disparity; African American (AA) men have a markedly higher risk of being diagnosed and of dying of prostate cancer compared to Caucasian American (CA) men. This disparity may be due to biologic differences associated with race or to sociologic factors, such as economic disparities or differences in access to care or interactions of all these factors. Differences in tumor gene expression and methylation might be associated with the poorer prognosis seen among AA men and may contribute to better understanding of these disparities and the delineation of new therapeutic targets. In order to study the effect of the tumor microenvironment on endothelial cells found in tissue from AA and CA patients with prostate cancer, we first established a method for the isolation of the endothelial cells from malignant and benign prostate tissue obtained at prostatectomy. We then conducted a pilot study of transcriptome and methylome analysis in 5 pairs of CD31+ endothelial cells isolated from paired samples of benign and malignant tissue from AA and CA patients with prostate cancer. We have identified 2,096 and 920 differentially expressed transcripts for the tumor versus normal in AA and CA group, respectively. However, only 140 transcripts are shared. Furthermore, a total of 2,248 transcripts show different level of expression change for tumor versus normal in samples with AA origin compared to samples with CA origin. Genome-wide DNA methylation profiling in the same endothelial samples have identified 18,093 differentially methylated loci in AA group, and 12,372 differentially methylated loci in CA group. Only a total of 1,324 loci are shared. Remarkably, there are a total of 20,164 loci with different level of methylation change for tumor versus normal in AA group compared to CA group. Integrative analysis of transcriptome and methylatome data showed that a large percentage of differentially expressed genes have loci whose methylation change is inversely correlated with gene expression change, and vice versa. Taken together, our pilot data, while preliminary, suggest the possibility that there is a potential racial difference in terms of differential expression and methylation between CA and AA endothelial cell populations. Future large studies are warranted to confirm our findings and further explore the role of race disparity in the delineation of novel therapeutic targets to be utilized clinically for prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4280. doi:1538-7445.AM2012-4280