Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung 404332, Taiwan.
Biomolecules. 2021 Dec 3;11(12):1826. doi: 10.3390/biom11121826.
DNA methylation plays important roles in prostate cancer (PCa) development and progression. African American men have higher incidence and mortality rates of PCa than other racial groups in U.S. The goal of this study was to identify differentially methylated CpG sites and genes between clinically defined aggressive and nonaggressive PCa in African Americans. We performed genome-wide DNA methylation profiling in leukocyte DNA from 280 African American PCa patients using Illumina MethylationEPIC array that contains about 860K CpG sties. There was a slight increase of overall methylation level (mean β value) with the increasing Gleason scores (GS = 6, GS = 7, GS ≥ 8, P for trend = 0.002). There were 78 differentially methylated CpG sites with P < 10 and 9 sites with P < 10 in the trend test. We also found 77 differentially methylated regions/genes (DMRs), including 10 homeobox genes and six zinc finger protein genes. A gene ontology (GO) molecular pathway enrichment analysis of these 77 DMRs found that the main enriched pathway was DNA-binding transcriptional factor activity. A few representative DMRs include HOXD8, SOX11, ZNF-471, and ZNF-577. Our study suggests that leukocyte DNA methylation may be valuable biomarkers for aggressive PCa and the identified differentially methylated genes provide biological insights into the modulation of immune response by aggressive PCa.
DNA 甲基化在前列腺癌（PCa）的发展和进展中起着重要作用。美国的非裔美国男性患 PCa 的发病率和死亡率比其他种族群体都高。本研究的目的是确定非裔美国人中临床定义的侵袭性和非侵袭性 PCa 之间差异甲基化的 CpG 位点和基因。我们使用包含约 860K CpG 位点的 Illumina MethylationEPIC 阵列，对 280 名非裔美国 PCa 患者的白细胞 DNA 进行了全基因组 DNA 甲基化谱分析。随着 Gleason 评分（GS = 6、GS = 7、GS≥8）的增加，整体甲基化水平（平均β值）略有升高（趋势检验 P = 0.002）。有 78 个 CpG 位点的甲基化差异具有统计学意义（P < 10），9 个位点在趋势检验中具有统计学意义（P < 10）。我们还发现了 77 个差异甲基化区域/基因（DMRs），包括 10 个同源盒基因和 6 个锌指蛋白基因。对这 77 个 DMRs 的基因本体（GO）分子途径富集分析发现，主要富集途径是 DNA 结合转录因子活性。一些有代表性的 DMR 包括 HOXD8、SOX11、ZNF-471 和 ZNF-577。我们的研究表明，白细胞 DNA 甲基化可能是侵袭性 PCa 的有价值的生物标志物，并且鉴定出的差异甲基化基因提供了关于侵袭性 PCa 调节免疫反应的生物学见解。
