Koowattanasuchat Sireemas, Ngernpimai Sawinee, Matulakul Piyaporn, Thonghlueng Janpen, Phanchai Witthawat, Chompoosor Apiwat, Panitanarak Uthumporn, Wanna Yupaporn, Intharah Thanapong, Chootawiriyasakul Kanokon, Anata Pimjai, Chaimnee Prajuab, Thanan Raynoo, Sakonsinsiri Chadamas, Puangmali Theerapong
Department of Physics, Faculty of Science, Khon Kaen University Khon Kaen 40002 Thailand
Department of Chemistry, Faculty of Science, Ramkhamhaeng University Bangkok 10240 Thailand.
RSC Adv. 2023 Jan 5;13(2):1301-1311. doi: 10.1039/d2ra05725e. eCollection 2023 Jan 3.
DNA methylation occurs when a methyl group is added to a cytosine (C) residue's fifth carbon atom, forming 5-methylcytosine (5-mC). Cancer genomes have a distinct methylation landscape (Methylscape), which could be used as a universal cancer biomarker. This study developed a simple, low-cost, and straightforward Methylscape sensing platform using cysteamine-decorated gold nanoparticles (Cyst/AuNPs), in which the sensing principle is based on methylation-dependent DNA solvation. Normal and cancer DNAs have distinct methylation profiles; thus, they can be distinguished by observing the dispersion of Cyst/AuNPs adsorbed on these DNA aggregates in MgCl solution. After optimising the MgCl, Cyst/AuNPs, DNA concentration, and incubation time, the optimised conditions were used for leukemia screening, by comparing the relative absorbance (Δ ). Following the DNA extraction from actual blood samples, this sensor demonstrated effective leukemia screening in 15 minutes with high sensitivity, achieving 95.3% accuracy based on the measurement by an optical spectrophotometer. To further develop for practical realisation, a smartphone assisted by machine learning was used to screen cancer patients, achieving 90.0% accuracy in leukemia screening. This sensing platform can be applied not only for leukemia screening but also for other cancers associated with epigenetic modification.
当甲基添加到胞嘧啶（C）残基的第五个碳原子上形成5-甲基胞嘧啶（5-mC）时，就会发生DNA甲基化。癌症基因组具有独特的甲基化图谱（甲基图谱），可作为通用的癌症生物标志物。本研究利用半胱胺修饰的金纳米颗粒（Cyst/AuNPs）开发了一种简单、低成本且直接的甲基图谱传感平台，其传感原理基于甲基化依赖的DNA溶剂化。正常DNA和癌症DNA具有不同的甲基化谱；因此，通过观察MgCl溶液中吸附在这些DNA聚集体上的Cyst/AuNPs的分散情况，可以区分它们。在优化了MgCl、Cyst/AuNPs、DNA浓度和孵育时间后，通过比较相对吸光度（Δ），将优化后的条件用于白血病筛查。从实际血液样本中提取DNA后，该传感器在15分钟内实现了高效的白血病筛查，灵敏度高，基于分光光度计测量的准确率达到95.3%。为了进一步实现实际应用，使用了由机器学习辅助的智能手机来筛查癌症患者，在白血病筛查中准确率达到90.0%。这种传感平台不仅可用于白血病筛查，还可用于其他与表观遗传修饰相关的癌症。
