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    An epigenetic classifier for early stage lung cancer

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    Author
    Su, Y.
    Fang, H.B.
    Jiang, F.
    Date
    2018
    Journal
    Clinical Epigenetics
    Publisher
    BioMed Central Ltd.
    Type
    Article
    
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    See at
    https://dx.doi.org/10.1186/s13148-018-0502-3
    Abstract
    Background: Methylated genes detected in sputum are promise biomarkers for lung cancer. Yet the current PCR technologies for quantification of DNA methylation and diagnostic value of the sputum biomarkers are not sufficient to be used for lung cancer early detection. The emerging droplet digital PCR (ddPCR) is a straightforward means for precise, direct, and absolute quantification of nucleic acids. Here, we investigate whether ddPCR can sensitively and robustly quantify DNA methylation in sputum for more precise diagnosis of lung cancer. Results: First, the analytic performance of methylation-specific ddPCR (ddMSP) and quantitative methylation-specific PCR (qMSP) is determined in methylated and unmethylated DNA samples. Second, 29 genes, previously proposed as potential sputum biomarkers for lung cancer, are analyzed by using ddMSP in a training set of 127 lung cancer patients and 159 controls. ddMSP has higher sensitivity, precision, and reproducibility for quantification of methylation compared with qMSP (all p < 0.05). A classifier comprising four sputum methylation biomarkers for lung cancer is developed by using ddMSP, producing 86.6% sensitivity and 90.6% specificity, independent of stage and histology of lung cancer (all p > 0.05). The classifier has higher accuracy compared with sputum cytology (88.8 vs. 70.6%, p < 0.01). The diagnostic performance is confirmed in a testing set of 89 cases and 107 controls. Conclusions: ddMSP is a robust tool for reliable quantification of DNA methylation in sputum, and the epigenetic classifier could help diagnose lung cancer at the early stage. Copyright 2018 The Author(s).
    Sponsors
    This study was supported in part by a grant for cancer research from Jiangsu Province Hospital of Nanjing University of Chinese Medicine (Y. S.)
    Keyword
    DdPCR
    Lungs--Cancer
    Diagnosis
    DNA Methylation
    Sputum
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047334488&doi=10.1186%2fs13148-018-0502-3&partnerID=40&md5=d5e741bbd751d71a9e0e4ea2d7034dd8; http://hdl.handle.net/10713/8890
    ae974a485f413a2113503eed53cd6c53
    10.1186/s13148-018-0502-3
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