Login to Access Video or Poster Abstract: MP87-09
Sources of Funding: Deane Prostate Health, Icahn School of Medicine at Mount Sinai. Both Shalini S Yadav and Kamlesh K Yadav are supported by the Prostate Cancer Foundation Young Investigator Awards.

Introduction

Prostate Cancer (PCa) is amongst the top five in cancer related death in men worldwide. Epidemiologically it varies with race and ethnicity. African American (AA) men not only have a higher incidence rate (~60%), but also ~2.5-times higher rate of mortality when compared to Caucasian men (CaM). In addition, there is diverse molecular heterogeneity in terms of mutations, gene expression, methylation patterns and copy number alterations in PCa. Therefore, it is of interest to identify the epigenetic and transcriptomic variation in African American and Caucasians.

Methods

The Cancer Genome Atlas (TCGA) dataset was used to investigate the variation in the biology of prostate cancer patients categorized on the basis of ethnicity. The study included large cohort of 333 primary prostate carcinoma patients that included 43 AA (13%) and 162 CaM (48%). We assessed and analyzed the differential methylation patterns amongst African Americans and Caucasians. Further, the genes that are differentially expressed in each methylation cluster were analyzed to identify the biological pathways that are significantly affected in both the races.

Results

We identified that out of four methylation clusters, AA predominantly belongs to methylation cluster 1 (20.9%) compared to CaM (9.9%). However, CaM (37%) preferentially belongs to methylation cluster 3 than AA (7%). Interestingly, the pathways involved with upregulated genes in methylation cluster 1 were associated with neuronal related pathway whereas, similar pathways were observed to be downregulated in methylation cluster 3. Comparatively, pathways associated with upregulated genes in cluster 3 include inflammation related pathways and hedgehog signaling pathways. Cell cycle signaling, DNA replication and Wnt signaling were predominantly associated with downregulated genes in methylation cluster 1.

Conclusions

The disparity in the molecular mechanism involved in the pathogenesis of prostate cancers in AA and CaM suggests diverse heterogeneity among different races. Variation of neuronal related pathway in different methylation clusters and their association with AA indicate its crucial role in racial disparity. Enrichment of neuronal signaling may reflect the more aggressive phenotype observed in prostate cancers of AA men. _x000D_ _x000D_

Funding

Deane Prostate Health, Icahn School of Medicine at Mount Sinai. Both Shalini S Yadav and Kamlesh K Yadav are supported by the Prostate Cancer Foundation Young Investigator Awards.