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    Development of a circulating miRNA assay to monitor tumor burden: From mouse to man.

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    Authors
    Greystoke, Alastair
    Ayub, Mahmood
    Rothwell, Dominic G
    Morris, Daniel
    Burt, Deborah J
    Hodgkinson, Cassandra L
    Morrow, Christopher J
    Smith, Nigel K
    Aung, Kyaw Lwin
    Valle, Juan W
    Carter, Louise
    Blackhall, Fiona H
    Dive, Caroline
    Brady, Ged
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    Affiliation
    Clinical & Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester
    Issue Date
    2015-10-28
    
    Metadata
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    Abstract
    Circulating miRNA stability suggests potential utility of miRNA based biomarkers to monitor tumor burden and/or progression, particularly in cancer types where serial biopsy is impractical. Assessment of miRNA specificity and sensitivity is challenging within the clinical setting. To address this, circulating miRNAs were examined in mice bearing human SCLC tumor xenografts and SCLC patient derived circulating tumor cell explant models (CDX). We identified 49 miRNAs using human TaqMan Low Density Arrays readily detectable in 10 μl tail vein plasma from mice carrying H526 SCLC xenografts that were low or undetectable in non-tumor bearing controls. Circulating miR-95 measured serially in mice bearing CDX was detected with tumor volumes as low as 10 mm(3) and faithfully reported subsequent tumor growth. Having established assay sensitivity in mouse models, we identified 26 miRNAs that were elevated in a stage dependent manner in a pilot study of plasma from SCLC patients (n = 16) compared to healthy controls (n = 11) that were also elevated in the mouse models. We selected a smaller panel of 10 previously reported miRNAs (miRs 95, 141, 200a, 200b, 200c, 210, 335#, 375, 429) that were consistently elevated in SCLC, some of which are reported to be elevated in other cancer types. Using a multiplex qPCR assay, elevated levels of miRNAs across the panel were also observed in a further 66 patients with non-small cell lung, colorectal or pancreatic cancers. The utility of this circulating miRNA panel as an early warning of tumor progression across several tumor types merits further evaluation in larger studies.
    Citation
    Development of a circulating miRNA assay to monitor tumor burden: From mouse to man. 2015: Mol Oncol
    Journal
    Molecular Oncology
    URI
    http://hdl.handle.net/10541/592962
    DOI
    10.1016/j.molonc.2015.10.004
    PubMed ID
    26654130
    Type
    Article
    Language
    en
    ISSN
    1878-0261
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.molonc.2015.10.004
    Scopus Count
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