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  • Review Article
  • Published:

Clinical relevance of circulating cell-free microRNAs in cancer

Nature Reviews Clinical Oncology volume 11, pages 145–156 (2014)Cite this article

Subjects

Key Points

  • Alterations in microRNAs (miRNAs) are involved in the pathogenesis of various types of human cancers, and because of the stability of tumour-derived cell-free microRNAs, these show potential as novel biomarkers

  • Cell-free miRNAs can be detected not only in plasma and serum, but also in other body fluids, such as urine and saliva, and serve as a non-invasive diagnostic tool

  • miRNAs also have an important role in chemo-resistance of cancer cells, and could be useful predictors of therapeutic response

  • Methods of detection, such as microarray analysis and deep-sequencing, enable a comprehensive profiling of cell-free miRNAs (including various isoforms) from low amounts of RNA samples

Abstract

Efficient patient management relies on early diagnosis of disease and monitoring of treatment. In this regard, much effort has been made to find informative, blood-based biomarkers for patients with cancer. Owing to their attributes—which are specifically modulated by the tumour—circulating cell-free microRNAs found in the peripheral blood of patients with cancer may provide insights into the biology of the tumour and the effects of therapeutic interventions. Moreover, the role of microRNAs in the regulation of different cellular processes points to their clinical utility as blood-based biomarkers and future therapeutic targets. MicroRNAs are optimal biomarkers owing to high stability under storage and handling conditions and their presence in blood, urine and other body fluids. In particular, detection of levels of microRNAs in blood plasma and serum has the potential for an earlier cancer diagnosis and to predict prognosis and response to therapy. This Review article considers the latest developments in the use of circulating microRNAs as prognostic and predictive biomarkers and discusses their utility in personalized medicine.

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Figure 1: Biogenesis and diverse functions of miRNAs.
Figure 2: Release of miRNAs from cells into the blood circulation.

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Acknowledgements

G.A.C. is The Alan M. Gewirtz Leukemia & Lymphoma Society Scholar. He was also supported as a Fellow at The University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar. Work in G.A.C.'s laboratory is supported in part by the US National Institutes of Health (NIH)/US National Cancer Institute (NCI) grants 1UH2TR00943-01 and 1R01 CA182905-01; a US Department of Defence Breast Cancer Idea Award; Developmental Research Awards in breast cancer, ovarian cancer, brain cancer, prostate cancer, multiple myeloma and leukaemia (P50 CA100632) as well as head and neck cancer (P50 CA097007) from the Specialized Programs of Research Excellence (SPOREs); by the CLL Global Research Foundation; a Sister Institution Network Fund (SINF) grant from the MD Anderson Cancer Centre and the German Cancer Research Centre (DKFZ) in chronic lymphocytic leukaemia; a SINF grant in colorectal cancer, the Laura and John Arnold Foundation; the RGK Foundation; and The Estate of C. G. Johnson Jr. K.P. is recipient of the European Research Council Advanced Investigator grant “DISSECT” (no. 269,081), and his work is supported by grants of the Deutsche Forschungsgemeinschaft (DFG), Federal Minister of Education and Science (BMBF) and Deutsche Krebshilfe. The authors apologize to all colleagues whose work was not cited because of space restrictions.

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Authors and Affiliations

  1. Department of Tumour Biology, Centre of Experimental Medicine, University Cancer Centre, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany

    Heidi Schwarzenbach & Klaus Pantel

  2. Department of Experimental Therapeutics and the Centre for RNA Interference and Non-Coding RNAs, The University of Texas, MD Anderson Cancer Center, South Campus Research Building 3, 1881 East Road, Houston, 77030, TX, USA

    Naohiro Nishida & George A. Calin

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  1. Heidi Schwarzenbach
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All authors researched data for article, contributed substantially to discussion of content, wrote, and reviewed and edited the manuscript before submission.

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Correspondence to Klaus Pantel.

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Supplementary Table 1

Diagnostic and prognostic value of circulating miRs in patients with different cancer entities) and 100 references (DOC 505 kb)

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Schwarzenbach, H., Nishida, N., Calin, G. et al. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol 11, 145–156 (2014). https://doi.org/10.1038/nrclinonc.2014.5

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