Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5G 1X5, Canada.
Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Epigenomics. 2020 Aug;12(15):1317-1332. doi: 10.2217/epi-2020-0173. Epub 2020 Sep 1.
We examined methylation changes in cell-free DNA (cfDNA) in metastatic castration-resistant prostate cancer (mCRPC) during treatment. Genome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. Alterations in methylation states of genes previously implicated in prostate cancer progression were observed and patients that maintained methylation changes throughout therapy tended to have a longer time to clinical progression. Importantly, we also report that markers associated with a highly aggressive form of the disease, neuroendocrine-CRPC, were associated with a faster time to clinical progression. Our findings highlight the potential of monitoring the cfDNA methylome during therapy in mCRPC, which may serve as predictive markers of response to androgen-targeting agents.
我们研究了转移性去势抵抗性前列腺癌（mCRPC）治疗过程中游离细胞 DNA（cfDNA）的甲基化变化。对接受雄激素靶向治疗的 mCRPC 患者连续采集的 cfDNA 样本进行了全基因组甲基化分析。观察到先前与前列腺癌进展相关的基因的甲基化状态发生改变，并且在整个治疗过程中保持甲基化改变的患者往往具有更长的临床进展时间。重要的是，我们还报告说，与神经内分泌-CRPC 这种侵袭性较强的疾病相关的标志物与临床进展时间较快相关。我们的研究结果强调了在 mCRPC 治疗过程中监测 cfDNA 甲基组的潜力，这可能成为雄激素靶向药物反应的预测标志物。
