title: Circulating microRNAs as stable blood-based markers for cancer detection.
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.
authors.affiliation: Divisions of Human Biology, Clinical Research, and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Mitchell
authors.forename: Rachael K
authors.initials: RK
authors.lastname: Parkin
authors.forename: Evan M
authors.initials: EM
authors.lastname: Kroh
authors.forename: Brian R
authors.initials: BR
authors.lastname: Fritz
authors.forename: Stacia K
authors.initials: SK
authors.lastname: Wyman
authors.forename: Era L
authors.initials: EL
authors.lastname: Pogosova-Agadjanyan
authors.forename: Amelia
authors.initials: A
authors.lastname: Peterson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Noteboom
authors.forename: Kathy C
authors.initials: KC
authors.lastname: O'Briant
authors.forename: April
authors.initials: A
authors.lastname: Allen
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Lin
authors.forename: Nicole
authors.initials: N
authors.lastname: Urban
authors.forename: Charles W
authors.initials: CW
authors.lastname: Drescher
authors.forename: Beatrice S
authors.initials: BS
authors.lastname: Knudsen
authors.forename: Derek L
authors.initials: DL
authors.lastname: Stirewalt
authors.forename: Robert
authors.initials: R
authors.lastname: Gentleman
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.forename: Peter S
authors.initials: PS
authors.lastname: Nelson
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Martin
authors.forename: Muneesh
authors.initials: M
authors.lastname: Tewari
mesh_terms: 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
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012334:RNA, Neoplasm; D012260:Ribonucleases