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基于 DNA-金纳米探针的集成生物传感技术用于血清 miRNA 的非侵入性液体活检:前列腺癌诊断的新前沿。

DNA-gold nanoprobe-based integrated biosensing technology for non-invasive liquid biopsy of serum miRNA: A new frontier in prostate cancer diagnosis.

机构信息

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.

Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA.

出版信息

Nanomedicine. 2022 Jul;43:102566. doi: 10.1016/j.nano.2022.102566. Epub 2022 May 13.

Abstract

The low specificity of prostate-specific antigen contributes to overdiagnosis and ov ertreatment of prostate cancer (PCa) patients. Hence, there is an urgent need for inclusive diagnostic platforms that could improve the diagnostic accuracy of PCa. Dysregulated miRNAs are closely associated with the progression and recurrence and have emerged as promising diagnostic and prognostic biomarkers for PCa. Nevertheless, simple, rapid, and ultrasensitive quantification of serum miRNAs is highly challenging. This study designed, synthesized, and demonstrated the practicability of DNA-linked gold nanoprobes (DNA-AuNPs) for the single-step quantification of miR-21/miR-141/miR-375. In preclinical study, the assay differented PCa Pten conditional knockout (Pten) mice compared to their age-matched Pten wild-type (Pten) control mice. In human sera, receiver operating characteristic (ROC) curve-based correlation analyses revealed clear discrimination between PCa patients from normal healthy controls using training and validation sets. Overall, we established integrated nano-biosensing technology for the PCR-free, non-invasive liquid biopsies of multiple miRNAs for PCa diagnosis.

摘要

前列腺特异性抗原的低特异性导致前列腺癌 (PCa) 患者的过度诊断和过度治疗。因此,迫切需要包容性的诊断平台,以提高 PCa 的诊断准确性。失调的 miRNA 与疾病的进展和复发密切相关,已成为 PCa 的有前途的诊断和预后生物标志物。然而,简单、快速、超灵敏地定量血清 miRNA 极具挑战性。本研究设计、合成并证明了 DNA 连接的金纳米探针 (DNA-AuNPs) 用于 miR-21/miR-141/miR-375 的一步定量的实用性。在临床前研究中,该检测方法区分了前列腺癌 Pten 条件性敲除 (Pten) 小鼠与它们年龄匹配的 Pten 野生型 (Pten) 对照小鼠。在人血清中,基于接受者操作特征 (ROC) 曲线的相关分析,使用训练和验证集清楚地区分了 PCa 患者和正常健康对照者。总体而言,我们建立了用于 PCa 诊断的无 PCR、非侵入性液体活检的集成纳米生物传感技术,可同时检测多种 miRNA。

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