Circulating microRNAs as stable blood-based markers for cancer detection

Patrick S. Mitchell(Fred Hutch Cancer Center), Rachael K. Parkin(Fred Hutch Cancer Center), Evan M. Kroh(Fred Hutch Cancer Center), Brian R. Fritz(Illumina (United States)), Stacia K. Wyman(Fred Hutch Cancer Center), Era L. Pogosova‐Agadjanyan(Fred Hutch Cancer Center), Amelia C. Peterson(Fred Hutch Cancer Center), Jennifer Noteboom(University of Washington), Kathy O'Briant(Fred Hutch Cancer Center), April N. Allen(Fred Hutch Cancer Center), Daniel W. Lin(University of Washington), Nicole Urban(Fred Hutch Cancer Center), Charles W. Drescher(Fred Hutch Cancer Center), Beatrice S. Knudsen(Fred Hutch Cancer Center), Derek L. Stirewalt(Fred Hutch Cancer Center), Robert Gentleman(Fred Hutch Cancer Center), Robert L. Vessella(University of Washington), Peter S. Nelson(Fred Hutch Cancer Center), Daniel Martin(Institute for Systems Biology), Muneesh Tewari(Fred Hutch Cancer Center)
Proceedings of the National Academy of Sciences
July 28, 2008
Cited by 7,944Open Access
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Abstract

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 ( approximately 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.


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