Epigenome-wide association study of prostate cancer in African American men identified differentially methylated genes.

Autor: Berglund A; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Yamoah K; Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Eschrich SA; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Falahat R; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Mulé JJ; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Kim S; Department of Radiation Oncology, Mayo Clinic Alix College of Medicine and Health Sciences, Jacksonville, Florida, USA., Matta J; Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University-School of Medicine, Ponce, Puerto Rico., Dutil J; Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University-School of Medicine, Ponce, Puerto Rico., Ruiz-Deya G; Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University-School of Medicine, Ponce, Puerto Rico., Ortiz Sanchez C; Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University-School of Medicine, Ponce, Puerto Rico., Wang L; Department of Tumor Biology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Park H; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Banerjee HN; Natural, Pharmacy and Health Sciences, Elizabeth City State University, Elizabeth City, North Carolina, USA., Lotan T; Johns Hopkins University, Baltimore, Maryland, USA., Barry KH; Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.; Program in Oncology, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA., Putney RM; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Kim SJ; Division of Pulmonology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Gwede C; Department of Health Outcome and Behavior, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Kresovich JK; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Kim Y; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Lin HY; Biostatistics and Data Science Program, School of Public Health, Louisiana State University School of Medicine, New Orleans, Louisiana, USA., Dhillon J; Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Chakrabarti R; Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida, USA., Park JY; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2024 Aug; Vol. 13 (16), pp. e70044.
DOI: 10.1002/cam4.70044
Abstrakt: Introduction: Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide.
Methods: This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array.
Results: Around 5,139 differentially methylated CpG-sites (q < 0.01, lΔβl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors.  Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors' total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG-sites (q < 0.05, lΔβl > .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA-C, and ADCYAP1, have previously been linked to tumor progression in PCa.
Conclusion: Several differentially methylated genes involved in immune-oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American-specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.
(© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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