一种多功能电化学生物传感器，用于检测循环 MicroRNA 对非小细胞肺癌的诊断,Small

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一种多功能电化学生物传感器，用于检测循环 MicroRNA 对非小细胞肺癌的诊断
Small ( IF 13.0 ) Pub Date : 2022-03-25 , DOI: 10.1002/smll.202200784
Fanyu Meng _{1,

2} , Wenjun Yu ₁ , Changqiang Chen ₃ , Susu Guo ₂ , Xiaoting Tian ₂ , Yayou Miao ₂ , Lifang Ma _{1,

2} , Xiao Zhang _{1,

2} , Yongchun Yu ₂ , Lin Huang _{1,

2} , Kun Qian ₄ , Jiayi Wang _{1,

2}

Affiliation

循环 microRNA (miRNA) 可用作非侵入性生物标志物，并且还发现在血液等体液中循环。失调的 miRNA 表达与包括非小细胞肺癌 (NSCLC) 在内的许多疾病有关，miRNA 检测有助于癌症诊断、预后和监测。在这项工作中，开发了一种通用的电化学生物传感系统，用于通过 DNAzyme 切割循环扩增和杂交链式反应 (HCR) 扩增检测 miRNA。被 Mn ^2+裂解靶向 DNAzyme，DNA-walker 可以沿着预先设计的 DNA 轨道移动，并有助于信号的转导和增强。对于电化学过程，通过 HCR 扩增触发了多个掺入 G-四链体的长双链 DNA (dsDNA/G-四链体) 结构的形成。G-quadruplex 的引入允许对低至 5.68 fM 的 miRNA 进行灵敏的测量，并具有良好的特异性。此外，通过分析 NSCLC 队列中的 miRNA，这种设计的策略显示出高效率（使用接受者操作特征 (ROC) 分析的曲线下面积 (AUC) 为 0.879），对 NSCLC 早期诊断（I 期）的敏感性为 80.0%。对于 NSCLC 和良性疾病的区分，该测定显示 AUC 为 0.907，优于六种临床可接受的蛋白质肿瘤标志物。所以，

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A Versatile Electrochemical Biosensor for the Detection of Circulating MicroRNA toward Non-Small Cell Lung Cancer Diagnosis

Circulating microRNAs (miRNAs) can be used as noninvasive biomarkers and are also found circulating in body fluids such as blood. Dysregulated miRNA expression is associated with many diseases, including non-small cell lung cancer (NSCLC), and the miRNA assay is helpful in cancer diagnosis, prognosis, and monitoring. In this work, a versatile electrochemical biosensing system is developed for miRNA detection by DNAzyme-cleavage cycling amplification and hybridization chain reaction (HCR) amplification. With cleavage by Mn²⁺ targeted DNAzyme, DNA-walker can move along the predesigned DNA tracks and contribute to the transduction and enhancement of signals. For the electrochemical process, the formation of multiple G-quadruplex-incorporated long double-stranded DNA (dsDNA/G-quadruplex) structures is triggered through HCR amplification. The introduction of G-quadruplex allows sensitive measurement of miRNA down to 5.68 fM with good specificity. Furthermore, by profiling miRNA in the NSCLC cohort, this designed strategy shows high efficiency (area under the curve (AUC) of 0.879 using receiver operating characteristic (ROC) analysis) with the sensitivity of 80.0% for NSCLC early diagnosis (stage I). For the discrimination of NSCLC and benign disease, the assay displays an AUC of 0.907, superior to six clinically-acceptable protein tumor markers. Therefore, this platform holds promise in clinical application toward NSCLC diagnosis and prognosis.

更新日期：2022-03-25

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