Toward Precision Medicine: A Cancer Molecular Subtyping Nano-Strategy for RNA Biomarkers in Tumor and Urine
Toward Precision Medicine: A Cancer Molecular Subtyping Nano-Strategy for RNA Biomarkers in Tumor and Urine
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DOI：
10.1002/smll.201602161
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发表时间：
2016-12-07
期刊：
影响因子：
13.3
通讯作者：
Trau, Matt
中科院分区：
文献类型：
--
作者：
Koo, Kevin M.;Wee, Eugene J. H.;Trau, Matt
癌症是一种异质性疾病，由于肿瘤发生、进展和转移的复杂性，表现为不同的分子亚型。精准医学的概念旨在通过结合诊断技术来表征每个癌症患者的分子亚型以进行定制治疗，从而利用这种癌症异质性。为了准确表征癌症分子亚型，目前已开发出一套多重生物测定法来检测多种致癌生物标志物。尽管当前的多重检测技术具有可靠性，但仍然需要新的策略来解决诸如测定时间长、协议复杂以及难以解释传统荧光读数的宽重叠光谱峰等限制。本文提出了一种快速（80 分钟）多重平台策略，用于根据 RNA 生物标志物谱对前列腺癌肿瘤和尿液样本进行亚型分型。这是通过将目标 RNA 生物标志物的快速多重等温逆转录重组酶聚合酶扩增 (RT-RPA) 与表面增强拉曼光谱 (SERS) 纳米标签相结合进行“一锅”读出来实现的。这是基于 RT-RPA/SERS 的平台的首次转化应用，用于多重癌症生物标志物检测，以满足临床需求。凭借 200 zmol（100 个拷贝）的出色灵敏度和特异性，我们相信该平台方法可能成为快速多重癌症亚型分析的有用工具。
Cancer is a heterogeneous disease which manifests as different molecular subtypes due to the complex nature of tumor initiation, progression, and metastasis. The concept of precision medicine aims to exploit this cancer heterogeneity by incorporating diagnostic technology to characterize each cancer patient's molecular subtype for tailored treatments. To characterize cancer molecular subtypes accurately, a suite of multiplexed bioassays have currently been developed to detect multiple oncogenic biomarkers. Despite the reliability of current multiplexed detection techniques, novel strategies are still needed to resolve limitations such as long assay time, complex protocols, and difficulty in interpreting broad overlapping spectral peaks of conventional fluorescence readouts. Herein a rapid (80 min) multiplexed platform strategy for subtyping prostate cancer tumor and urine samples based on their RNA biomarker profiles is presented. This is achieved by combining rapid multiplexed isothermal reverse transcription-recombinase polymerase amplification (RT-RPA) of target RNA biomarkers with surface-enhanced Raman spectroscopy (SERS) nanotags for "one-pot" readout. This is the first translational application of a RT-RPA/SERS-based platform for multiplexed cancer biomarker detection to address a clinical need. With excellent sensitivity of 200 zmol (100 copies) and specificity, we believed that this platform methodology could be a useful tool for rapid multiplexed subtyping of cancers.