乳腺癌
三阴性乳腺癌
计算生物学
细胞外小泡
清脆的
癌症
癌症研究
生物
医学
内科学
基因
生物化学
细胞生物学
作者
Shuang Yang,Liang Zhou,Zhikai Fang,Ying Wang,Guchun Zhou,Xi Jin,Ya Cao,Jing Zhao
出处
期刊:ACS Sensors
[American Chemical Society]
日期:2024-04-15
标识
DOI:10.1021/acssensors.4c00491
摘要
Breast cancer is one of the most diagnosed cancers worldwide. Precise diagnosis and subtyping have important significance for targeted therapy and prognosis prediction of breast cancer. Herein, we design a proximity-guaranteed DNA machine for accurate identification of breast cancer extracellular vesicles (EVs), which is beneficial to explore the subtype features of breast cancer. In our design, two proximity probes are located close on the same EV through specific recognition of coexisting surface biomarkers, thus being ligated with the help of click chemistry. Then, the ligated product initiates the operation of a DNA machine involving catalytic hairpin assembly and clusters of regularly interspaced short palindromic repeats (CRISPR)-Cas12a-mediated trans-cleavage, which finally generates a significant response that enables the identification of EVs expressing both biomarkers. Principle-of-proof studies are performed using EVs derived from the breast cancer cell line BT474 as the models, confirming the high sensitivity and specificity of the DNA machine. When further applied to clinical samples, the DNA machine is shown to be capable of not only distinguishing breast cancer patients with special subtypes but also realizing the tumor staging regarding the disease progression. Therefore, our work may provide new insights into the subtype-based diagnosis of breast cancer as well as identification of more potential therapeutic targets in the future.
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