Circulating microRNAs as stable blood-based markers for cancer detection

Circulating microRNAs as stable blood-based markers for cancer detection
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DOI:
10.1073/pnas.0804549105
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发表时间:
2008-07-29
影响因子:
11.1
通讯作者:
Tewari, Muneesh
Tewari, Muneesh
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mitchell, Patrick S.;Parkin, Rachael K.;Tewari, Muneesh

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迫切需要用于检测常见上皮恶性肿瘤的改进方法,以降低由癌症引起的全球发病率和死亡率。微小RNA(microRNAs,miRNAs)是一种小的(约22 nt)调控RNA,在癌症中经常发生失调,并有望作为肿瘤分类和诊断的组织标志物。我们在这里表明,miRNA是存在于人类血浆中的一个非常稳定的形式,是从内源性RNA酶活性的保护。源自人前列腺癌异种移植物的miRNA进入循环,在血浆中容易测量,并且可以稳健地区分异种移植小鼠与对照。这一概念延伸到人类癌症,其中miR-141(前列腺癌中表达的miRNA)的血清水平可以区分前列腺癌患者和健康对照。我们的研究结果确立了血清或血浆中肿瘤源性miRNA的测量作为基于血液的人类癌症检测的重要方法。
improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small (approximate to 22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.