Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
Genomics. 2019 Jan;111(1):10-16. doi: 10.1016/j.ygeno.2016.02.004. Epub 2016 Feb 21.
This study examined whether differential DNA methylation is associated with clinical features of more aggressive disease at diagnosis and prostate cancer recurrence in African American men, who are more likely to die from prostate cancer than other populations. Tumor tissues from 76 African Americans diagnosed with prostate cancer who had radical prostatectomy as their primary treatment were profiled for epigenome-wide DNA methylation levels. Long-term follow-up identified 19 patients with prostate cancer recurrence. Twenty-three CpGs were differentially methylated (FDR q≤0.25, mean methylation difference≥0.10) in patients with vs. without recurrence, including CpGs in GCK, CDKL2, PRDM13, and ZFR2. Methylation differences were also observed between men with metastatic-lethal prostate cancer vs. no recurrence (five CpGs), regional vs. local pathological stage (two CpGs), and higher vs. lower tumor aggressiveness (one CpG). These results indicate that differentially methylated CpG sites identified in tumor tissues of African American men may contribute to prostate cancer aggressiveness.
本研究旨在探讨在被诊断为更具侵袭性疾病的临床特征和前列腺癌复发方面,DNA 甲基化是否存在差异,而非洲裔美国男性比其他人群更有可能死于前列腺癌。对 76 名接受根治性前列腺切除术作为主要治疗方法的被诊断患有前列腺癌的非洲裔美国人的肿瘤组织进行了全基因组 DNA 甲基化水平的特征分析。长期随访确定了 19 名前列腺癌复发患者。在有和没有复发的患者中,有 23 个 CpG 表现出差异甲基化(FDR q≤0.25,平均甲基化差异≥0.10),包括 GCK、CDKL2、PRDM13 和 ZFR2 中的 CpG。在转移性致命性前列腺癌与无复发(五个 CpG)、局部与局部病理分期(两个 CpG)以及肿瘤侵袭性较高与较低(一个 CpG)的男性之间,也观察到了甲基化差异。这些结果表明,在非洲裔美国男性的肿瘤组织中鉴定出的差异甲基化 CpG 位点可能与前列腺癌的侵袭性有关。