Cited by 7,969MicroRNA in disease regulationExtracellular vesicles in diseaseCancer Genomics and Diagnostics

Circulating microRNAs as stable blood-based markers for cancer detection

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Mitchell, Patrick S., Parkin, Rachael K., Kroh, Evan M., Fritz, Brian R., Wyman, Stacia K., Pogosova-Agadjanyan, Era L., Peterson, Amelia, Noteboom, Jennifer +12 more·2008·Proceedings of the National Academy of Sciences

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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  • Extracellular miRNAs are highly stable, resisting degradation at room temperature for up to 4 days and in deleterious conditions such as boiling, multiple freeze-thaw cycles, and high or low pH.

    “Contrary to cellular RNA species, extracellular miRNAs are highly stable, resisting degradation at room temperature for up to 4 days and in deleterious conditions such as boiling, multiple freeze-thaw cycles, and high or low pH (117, 124).”

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Authors
Mitchell, P. S., Parkin, R. K., Kroh, E. M., Fritz, B. R., Wyman, S. K., Pogosova-Agadjanyan, E. L., Peterson, A., Noteboom, J., O'Briant, K. C., Allen, A., Lin, D. W., Urban, N., Drescher, C. W., Knudsen, B. S., Stirewalt, D. L., Gentleman, R., Vessella, R. L., Nelson, P. S., Martin, D. B., & Tewari, M.
Affiliations
  • Fred Hutch Cancer Center (US)
  • Illumina (United States) (US)
  • Clinical Research, and
  • University of Washington (US)
  • Institute for Systems Biology (US)
Venue
Proceedings of the National Academy of Sciences
Published
2008-07-29
Volume
105
Issue
30
Pages
10513-10518
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2115093090
Cited by
7,969
References
28
Citations by year
2026: 202 · 2025: 252 · 2024: 270 · 2023: 392 · 2022: 409 · 2021: 513 · 2020: 564 · 2019: 548 · 2018: 564 · 2017: 586 · 2016: 621 · 2015: 693 · 2014: 646 · 2013: 599 · 2012: 446
FWCI
74.94
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Fondation pour la Recherche Médicale
  • National Institutes of Health (5p50ca083636-15)
  • National Cancer Institute (P50-CA083636, CA 83636, P50 CA83636, P01CA085859, P50-CA97186, P50CA097186)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK56465, P30DK056465)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
circulating microRNAs, cancer detection, miR-141, prostate cancer, xenografts, serum biomarkers
MeSH terms
Animals, Cloning, Molecular, Humans, Male, Neoplasm Transplantation, Neoplasms, Prostatic Neoplasms, Ribonucleases, RNA, Neoplasm, Sensitivity and Specificity, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Gene Expression Profiling, MicroRNAs, Mice

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