Luo Bin, Zhou Juan, Li Zhigui, Song Jiajia, An Peng, Zhang Huinan, Chen Yi, Lan Fang, Ying Binwu, Wu Yao
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, People's Republic of China.
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Anal Chem. 2022 Apr 26;94(16):6261-6270. doi: 10.1021/acs.analchem.2c00104. Epub 2022 Apr 11.
DNA methylation analysis holds great promise in the whole process management of cancer early screening, diagnosis, and prognosis monitoring. Nevertheless, accurate detection of target methylated DNA, especially its methylation ratio in the genome, remains challenging. Herein, we report for the first time an integrated strategy of target-induced nanoparticle-coupling and site-specific base oxidation damage for DNA methylation analysis with the assistance of well-designed nanosensors. The ultrahigh sensitivity for detecting target methylated DNA as low as 32 × 10 M and high specificity for distinguishing 0.001% methylation ratio are achieved by this proposed strategy without amplification operations. Notably, the precise quantification of target DNA methylation ratio has been achieved for the first time. Through quantitative detection of target methylated DNA and methylation ratio, this proposed strategy could reliably diagnose and monitor cancer progression and treatment responses for colorectal cancer, which is superior to the clinical kit. It is anticipated that the proposed strategy has attractive application prospects in early diagnosis and monitoring for colorectal cancer and other various diseases.
DNA甲基化分析在癌症早期筛查、诊断及预后监测的全过程管理中具有巨大潜力。然而，准确检测目标甲基化DNA，尤其是其在基因组中的甲基化比例，仍然具有挑战性。在此，我们首次报道了一种集成策略，即在精心设计的纳米传感器的辅助下，通过目标诱导的纳米颗粒偶联和位点特异性碱基氧化损伤进行DNA甲基化分析。该策略无需扩增操作，即可实现对低至32×10⁻⁹ M的目标甲基化DNA的超高灵敏度检测以及对0.001%甲基化比例的高特异性区分。值得注意的是，首次实现了对目标DNA甲基化比例的精确定量。通过对目标甲基化DNA和甲基化比例的定量检测，该策略能够可靠地诊断和监测结直肠癌的癌症进展及治疗反应，优于临床试剂盒。预计该策略在结直肠癌及其他多种疾病的早期诊断和监测中具有诱人的应用前景。
