非洲血统的男性在全球范围内前列腺癌 (PCa) 的发病率和死亡率最高。本研究旨在确定 121 名非裔美国患者的肿瘤与邻近正常前列腺癌以及侵袭性前列腺癌与惰性前列腺癌之间的差异甲基化基因。使用人类 Illumina 甲基化 EPIC V1 阵列评估肿瘤 DNA 中的表观基因组范围的 DNA 甲基化模式。在比较正常与肿瘤时，识别出大约 5,139 个差异甲基化 CpG 位点 (q < 0.01，lΔβl > 0.2)，总体趋势前列腺肿瘤中的高甲基化。  与邻近正常组织相比，在前列腺肿瘤中检测到多个代表性差异甲基化区域 (DMR)，包括免疫相关基因，如 CD40、Galectin3、OX40L 和 STING。基于表观遗传时钟模型，我们观察到肿瘤的干细胞分裂总数和干细胞分裂率显着高于邻近的正常组织。关于 PCa 侵袭性，当将级别组 (GG)1 与 GG4/5 进行比较时，确定了 2,061 个差异甲基化 CpG 位点 (q < 0.05，lΔβl > .05)。在这 2,061 个 CpG 位点中，有 155 个探针在多次比较中始终显着。在这些基因中，一些免疫系统基因，如 COL18A1、S100A2、ITGA4、HLA-C 和 ADCYAP1，先前已被认为与 PCa 的肿瘤进展有关。几个差异甲基化基因参与与疾病风险或侵袭性相关的免疫肿瘤学途径被识别出来。此外，还确定了 261 个非裔美国人特有的与 PCa 风险相关的差异甲基化基因。这些结果可以揭示导致非裔美国人人口中 PCa 差异的潜在机制。© 2024 作者。约翰·威利出版的癌症医学

Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide.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.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.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.