Abstract C001: Effective visualization of methylation changes in prostate cancer among African American men

Abstract

Abstract Epigenetic modification, involving changes in the methylation of genes, play a key role in the molecular changes seen in many cancers, with prostate cancer (PCa) being one of them. These changes include both hyper-methylation, where genes are silenced and hypo-methylation where genes are over-expressed in tumors. Changes of methylation have also been linked to both drug-resistance and immune-evasion. We will in this work present a visualization suite that we have developed in our analysis of an in-house cohort of adjacent normal and prostate tumor tissue samples from men with African American ancestry (AA). We demonstrate significant changes in immune synapse genes in PCa using a principal component model that describe the dysregulation of both co-stimulatory genes and immune checkpoint genes. We also demonstrate significant changes in STING and changes in immune cell content between adjacent normal and tumor tissue. Treg and B memory cells are increase in tumor tissue, while there is a lower amount of naïve CD4 T cells and naïve B cells. Furthermore, we show that hyper-methylation occurs in many PCa samples, with multiple immune genes being silenced. The degree of hyper-methylation is shown on both a global and a focal view, with Chromosome 17 being most affected by hyper-methylation and zooming in at a region including RARA, IGFBP4, STAT5A, CAVIN1, PLEKHH3, RND2;VAT1, TMEM106A, and DHX8;ETV4 genes. We also compare our results from African American patients to a European cohort, demonstrating an overall similarity in methylation changes but also identifies unique methylation of genes, including GLRX, IFFO1, RASSF1, GEFT that are hyper-methylated in our PCa AA cohort. Additionally, we identify different categories of genes based on their methylation changes across PCa AA samples with different Gleason score. Using a Sankey graph, we classify significant CpG-probes into 8 different categories, describing both hyper- and hypo-methylation and if the changes are seen as a continues change between the different grades area more threshold like. Key genes include SEPT9, CCND2, TMHLE, and SPARCL1 being hyper methylation in tumors with a higher Gleason score, while CDH4, PRDM16, CSMD1, and IFI16 show hypo-methylation in higher Gleason score tumors. We also see an increase of Treg immune cells in PCa samples with high Gleason score. In conclusion, the visualization presented in this study provides an effective way to better understand the epigenetic changes seen in PCa AA men and can potentially also lead to a better understanding of the mechanisms contributing to PCa disparities in the AA population. Citation Format: Anders Berglund, Ryan M. Putney, Kosj Yamoah, Hyun Park, Jong Y. Park. Effective visualization of methylation changes in prostate cancer among African American men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C001.