CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
Shanghai Institute of Microsystem and information Technology, Chinese Academy of Sciences, Shanghai, 200050, China.
Nano Lett. 2020 Oct 14;20(10):7028-7035. doi: 10.1021/acs.nanolett.0c01898. Epub 2020 Sep 10.
Epigenetic alterations hold great promise as biomarkers for early stage cancer diagnosis. Nevertheless, direct identification of rare methylated DNA in the genome remains challenging. Here, we report an ultrasensitive framework nucleic acid-based electrochemical sensor for quantitative and highly selective analysis of DNA methylation. Notably, we can detect 160 fg of methylated DNA in million-fold unmethylated DNA samples using this electrochemical methylation-specific polymerase chain reaction (E-MSP) method. The high sensitivity of E-MSP enables one-step detection of low-abundance methylation at two different genes in patient serum samples. By using a combination test with two methylation alterations, we achieve high accuracy and sensitivity for reliable differentiation of prostate cancer and benign prostate hypertrophy (BPH). This new method sheds new light on translational use in early cancer diagnosis and in monitoring patients' responses to therapeutic agents.
表观遗传改变作为早期癌症诊断的生物标志物具有很大的潜力。然而，直接识别基因组中罕见的甲基化 DNA 仍然具有挑战性。在这里，我们报告了一种基于超灵敏框架核酸的电化学传感器，用于定量和高度选择性地分析 DNA 甲基化。值得注意的是，我们可以使用这种电化学甲基化特异性聚合酶链反应（E-MSP）方法，在百万倍未甲基化的 DNA 样本中检测到 160 fg 的甲基化 DNA。E-MSP 的高灵敏度能够在患者血清样本中一步检测到两个不同基因的低丰度甲基化。通过与两种甲基化改变的联合测试，我们实现了高准确性和灵敏度，可可靠地区分前列腺癌和良性前列腺增生（BPH）。这种新方法为癌症早期诊断和监测患者对治疗药物的反应的转化应用提供了新的思路。
