Patrick S. Mitchell1, Rachael K. Parkin2,3, Evan M. Kroh2,3, Brian R. Fritz2,3,4, Stacia K. Wyman2,3, Era L. Pogosova‐Agadjanyan3, Amelia C. Peterson2,3, Jennifer Noteboom5, Kathy O'Briant6, April N. Allen6, Daniel W. Lin5,7,6, Nicole Urban6, Charles W. Drescher6, Beatrice S. Knudsen6, Derek L. Stirewalt3, Robert Gentleman6, Robert L. Vessella5,7, Peter S. Nelson2,3, Daniel Martin3,8,9, Muneesh Tewari2,3
1Divisions of Human Biology, Clinical Research, and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
2Divisions of †Human Biology,
3Fred Hutchinson Cancer Research Center
4Illumina
5Department of Urology, University of Washington, Seattle, WA 98195; and
6Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;
7Department of Veterans Affairs, Puget Sound Health Care System, Seattle, WA 98108
8Institute for Systems Biology
9Institute for Systems Biology, Seattle, WA 98103
Tóm tắt
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 (≈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.
