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Clinical Potential of DNA Methylation in Gastric Cancer: A Meta-Analysis

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  • Nur Sabrina Sapari
  • Marie Loh
  • Aparna Vaithilingam
  • Richie Soong

Abstract

Background: Accumulating evidence indicates aberrant DNA methylation is involved in gastric tumourigenesis, suggesting it may be a useful clinical biomarker for the disease. The aim of this study was to consolidate and summarize published data on the potential of methylation in gastric cancer (GC) risk prediction, prognostication and prediction of treatment response. Methods: Relevant studies were identified from PubMed using a systematic search approach. Results were summarized by meta-analysis. Mantel-Haenszel odds ratios were computed for each methylation event assuming the random-effects model. Results: A review of 589 retrieved publications identified 415 relevant articles, including 143 case-control studies on gene methylation of 142 individual genes in GC clinical samples. A total of 77 genes were significantly differentially methylated between tumour and normal gastric tissue from GC subjects, of which data on 62 was derived from single studies. Methylation of 15, 4 and 7 genes in normal gastric tissue, plasma and serum respectively was significantly different in frequency between GC and non-cancer subjects. A prognostic significance was reported for 18 genes and predictive significance was reported for p16 methylation, although many inconsistent findings were also observed. No bias due to assay, use of fixed tissue or CpG sites analysed was detected, however a slight bias towards publication of positive findings was observed. Conclusions: DNA methylation is a promising biomarker for GC risk prediction and prognostication. Further focused validation of candidate methylation markers in independent cohorts is required to develop its clinical potential.

Suggested Citation

  • Nur Sabrina Sapari & Marie Loh & Aparna Vaithilingam & Richie Soong, 2012. "Clinical Potential of DNA Methylation in Gastric Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 7(4), pages 1-8, April.
  • Handle: RePEc:plo:pone00:0036275
    DOI: 10.1371/journal.pone.0036275
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    Cited by:

    1. Jundong Gu & Yanjun Wen & Siwei Zhu & Feng Hua & Hui Zhao & Hongrui Xu & Jiacong You & Linlin Sun & Weiqiang Wang & Jun Chen & Qinghua Zhou, 2013. "Association between P16INK4a Promoter Methylation and Non-Small Cell Lung Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(4), pages 1-10, April.
    2. Zongyue Zeng & Jiangen Wang & Liuyang Zhao & Ping Hu & Hailong Zhang & Xi Tang & Dali He & Shifu Tang & Zhaofang Zeng, 2013. "Potential Role of microRNA-21 in the Diagnosis of Gastric Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(9), pages 1-7, September.
    3. Zhang Lou-Qian & Yin Rong & Li Ming & Yang Xin & Jiang Feng & Xu Lin, 2013. "The Prognostic Value of Epigenetic Silencing of p16 Gene in NSCLC Patients: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-7, January.

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