期刊
SMALL
卷 18, 期 22, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202200784
关键词
DNAzymes; early diagnosis; hybridization chain reaction; lung cancer; microRNAs
类别
资金
- National Key R&D Program of China [2021YFA0910100, 2021YFF0703500, 2017YFE0124400, 2017YFC0909000]
- Shanghai Institutions of Higher Learning [2021-01-07-00-02-E00083]
- Shanghai Rising-Star Programme [19QA1404800]
- Innovation Group Project of Shanghai Municipal Health Commission [2019CXJQ03, 20194Y0317]
- Innovation Research Plan by the Shanghai Municipal Education Commission [ZXWF082101]
- Science and Technology Commission of Shanghai Municipality [21YF1443000]
- National Research Center for Translational Medicine Shanghai [TMSK-2021-124, NRCTM(SH)-2021-06]
- Medical-Engineering Joint Funds of Shanghai Jiao Tong University [YG2019QNA44, YG2021ZD09, YG2022QN107]
In this study, a versatile electrochemical biosensing system using DNAzyme-cleavage cycling amplification and hybridization chain reaction (HCR) amplification was developed for miRNA detection. The platform showed high sensitivity and specificity, and demonstrated good performance in early diagnosis and discrimination of non-small cell lung cancer (NSCLC).
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.
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