Circulating microRNAs as stable blood-based markers for cancer detection.
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.
Mitchell
Patrick S
PS
Divisions of Human Biology, Clinical Research, and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Parkin
Rachael K
RK
Kroh
Evan M
EM
Fritz
Brian R
BR
Wyman
Stacia K
SK
Pogosova-Agadjanyan
Era L
EL
Peterson
Amelia
A
Noteboom
Jennifer
J
O'Briant
Kathy C
KC
Allen
April
A
Lin
Daniel W
DW
Urban
Nicole
N
Drescher
Charles W
CW
Knudsen
Beatrice S
BS
Stirewalt
Derek L
DL
Gentleman
Robert
R
Vessella
Robert L
RL
Nelson
Peter S
PS
Martin
Daniel B
DB
Tewari
Muneesh
M
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics; D012334:RNA, Neoplasm / Q000097:blood / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012334:RNA, Neoplasm; D012260:Ribonucleases