Sun Li-Yue, Du Zi-Ming, Liu Yu-Ying, Li Yan-Hong, Liu Xiao-Min, Wang Ting, Shao Jian-Yong
State Key Laboratory of Oncology in South China, Guangzhou 510060, China.
Collaborative Innovation Centre for Cancer Medicine, Guangzhou 510060, China.
Cancers (Basel). 2021 Feb 7;13(4):664. doi: 10.3390/cancers13040664.
Prior research has established an electrochemical method based on the differential adsorption capacity of gold surfaces with different methylated DNA degrees and found that this method might be valuable for cancer diagnosis by detecting circulating free DNA methylation. However, further investigation on the underlying mechanism and validation of its diagnostic and prognostic values in a large cohort of malignant tumors was limited. We found that DNA with different methylation levels formed particles of diverse sizes on the gold surface. Hydrophobic bonds played a significant role in the binding process of methylated DNA to the gold surface. The detection condition of an adsorption time of 10 min and temperature of 20 °C was optimal. In a large cohort of plasma samples from the patients with different malignant tumors, as well as normal individuals, we found that the electrochemical detection method based on the differential adsorption capacity of methylated DNA degree on a gold surface could be used as a noninvasive tool for malignant tumor diagnosis and prognostic evaluation. The diagnostic efficiency of this method in malignant tumors was even slightly better than that of the current tumor biomarkers widely used in routine clinical practice (circulating free DNA (cfDNA) vs. carcinoembryonic antigen (CEA), 0.8131 vs. 0.7191 and cfDNA vs. CA19-9, 0.7687 vs. 0.6693).
先前的研究基于不同甲基化程度的DNA在金表面的差异吸附能力建立了一种电化学方法，并发现该方法通过检测循环游离DNA甲基化可能对癌症诊断具有重要价值。然而，对其潜在机制的进一步研究以及在大量恶性肿瘤队列中对其诊断和预后价值的验证是有限的。我们发现不同甲基化水平的DNA在金表面形成大小各异的颗粒。疏水键在甲基化DNA与金表面的结合过程中起重要作用。吸附时间为10分钟、温度为20℃的检测条件是最佳的。在来自不同恶性肿瘤患者以及正常个体的大量血浆样本队列中，我们发现基于甲基化DNA程度在金表面的差异吸附能力的电化学检测方法可作为恶性肿瘤诊断和预后评估的非侵入性工具。该方法在恶性肿瘤中的诊断效率甚至略优于目前在常规临床实践中广泛使用的肿瘤生物标志物（循环游离DNA（cfDNA）与癌胚抗原（CEA）相比，分别为0.8131和0.7191；cfDNA与CA19-9相比，分别为0.7687和0.6693）。
