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Diagnostic Performance of DNA Hypermethylation Markers in Peripheral Blood for the Detection of Colorectal Cancer: A Meta-Analysis and Systematic Review

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  • Bingsheng Li
  • Aihua Gan
  • Xiaolong Chen
  • Xinying Wang
  • Weifeng He
  • Xiaohui Zhang
  • Renxiang Huang
  • Shuzhu Zhou
  • Xiaoxiao Song
  • Angao Xu

Abstract

DNA hypermethylation in blood is becoming an attractive candidate marker for colorectal cancer (CRC) detection. To assess the diagnostic accuracy of blood hypermethylation markers for CRC in different clinical settings, we conducted a meta-analysis of published reports. Of 485 publications obtained in the initial literature search, 39 studies were included in the meta-analysis. Hypermethylation markers in peripheral blood showed a high degree of accuracy for the detection of CRC. The summary sensitivity was 0.62 [95% confidence interval (CI), 0.56–0.67] and specificity was 0.91 (95% CI, 0.89–0.93). Subgroup analysis showed significantly greater sensitivity for the methylated Septin 9 gene (SEPT9) subgroup (0.75; 95% CI, 0.67–0.81) than for the non-methylated SEPT9 subgroup (0.58; 95% CI, 0.52–0.64). Sensitivity and specificity were not affected significantly by target gene number, CRC staging, study region, or methylation analysis method. These findings show that hypermethylation markers in blood are highly sensitive and specific for CRC detection, with methylated SEPT9 being particularly robust. The diagnostic performance of hypermethylation markers, which have varied across different studies, can be improved by marker optimization. Future research should examine variation in diagnostic accuracy according to non-neoplastic factors.

Suggested Citation

  • Bingsheng Li & Aihua Gan & Xiaolong Chen & Xinying Wang & Weifeng He & Xiaohui Zhang & Renxiang Huang & Shuzhu Zhou & Xiaoxiao Song & Angao Xu, 2016. "Diagnostic Performance of DNA Hypermethylation Markers in Peripheral Blood for the Detection of Colorectal Cancer: A Meta-Analysis and Systematic Review," PLOS ONE, Public Library of Science, vol. 11(5), pages 1-13, May.
    • Handle: RePEc:plo:pone00:0155095
    DOI: 10.1371/journal.pone.0155095
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    1. Ben Dwamena, 2007. "MIDAS: Stata module for meta-analytical integration of diagnostic test accuracy studies," Statistical Software Components S456880, Boston College Department of Economics, revised 05 Feb 2009.
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    Cited by:

    1. Afsaneh Mojtabanezhad Shariatpanahi & Maryam Yassi & Mehdi Nouraie & Amirhossein Sahebkar & Fatemeh Varshoee Tabrizi & Mohammad Amin Kerachian, 2018. "The importance of stool DNA methylation in colorectal cancer diagnosis: A meta-analysis," PLOS ONE, Public Library of Science, vol. 13(7), pages 1-18, July.

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