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. 2022 Jul;14(13):811-822. doi: 10.2217/epi-2022-0103. Epub 2022 Jul 12.
This study examined circulating cell-free DNA (cfDNA) biomarkers associated with androgen treatment resistance in metastatic castration resistance prostate cancer (mCRPC). We designed a panel of nine candidate cfDNA methylation markers using droplet digital PCR (Methyl-ddPCR) and assessed methylation levels in sequentially collected cfDNA samples from patients with mCRPC. Increased cfDNA methylation in eight out of nine markers during androgen-targeted treatment correlated with a faster time to clinical progression. Cox proportional hazards modeling and logistic regression analysis further confirmed that higher cfDNA methylation during treatment was significantly associated with clinical progression. Overall, our findings have revealed a novel methylated cfDNA marker panel that could aid in the clinical management of metastatic prostate cancer.
本研究旨在探讨与转移性去势抵抗性前列腺癌（mCRPC）雄激素治疗抵抗相关的循环无细胞 DNA（cfDNA）生物标志物。我们使用液滴数字 PCR（Methyl-ddPCR）设计了一组九个候选 cfDNA 甲基化标志物，并评估了 mCRPC 患者连续采集的 cfDNA 样本中的甲基化水平。在雄激素靶向治疗期间，九个标志物中的八个标志物的 cfDNA 甲基化水平升高与更快的临床进展时间相关。Cox 比例风险模型和逻辑回归分析进一步证实，治疗期间更高的 cfDNA 甲基化与临床进展显著相关。总的来说，我们的研究结果揭示了一个新的甲基化 cfDNA 标志物面板，可能有助于转移性前列腺癌的临床管理。
