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The Prognostic Role of RASSF1A Promoter Methylation in Breast Cancer: A Meta-Analysis of Published Data

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  • Yong Jiang
  • Lin Cui
  • Wen-de Chen
  • Shi-hai Shen
  • Li-dong Ding

Abstract

Purpose: Epigenetic alterations have been investigated as prognostic indicators in breast cancer but their translation into clinical practice has been impeded by a lack of appropriate validation. We present the results of a meta-analysis of the associations between RASSF1A promoter methylation status and both disease free survival (DFS) and overall survival (OS) in female breast cancer. Methods: Eligible studies were identified through searching the PubMed, Web of Science and Embase databases. Studies were pooled and summary hazard ratios (HR) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also carried out to evaluate publication bias. Results: A total of 1795 patients from eight studies were included in the meta-analysis. There are eight studies which investigated DFS in 1795 cases. The relative hazard estimates ranged from 1.77–5.64 with a combined HR of 2.75 (95%CI 1.96–3.84). The HR of RASSF1A promoter methylation on DFS adjusted for other potential prognostic factors was 2.54 (95%CI 1.77–3.66). There has been five trials which analyzed the associations of RASSF1A promoter methylation status with OS in 1439 patients. The hazard estimates ranged from 1.21–6.90 with a combined random-effects estimates of 3.47 (95%CI 1.44–8.34). OS reported in multivariate analysis was evaluated in four series comprising 1346 cases and the summarized random-effects HR estimate was 3.35 (95%CI 1.14–9.85). Additionally, no publication bias was detected for both OS and DFS. Conclusion: The results of this meta-analysis suggest that RASSF1A promoter hypermethylation confers a higher risk of relapse and a worse survival in patients with breast cancer. Large prospective studies are now needed to establish the clinical utility of RASSF1A promoter methylation.

Suggested Citation

  • Yong Jiang & Lin Cui & Wen-de Chen & Shi-hai Shen & Li-dong Ding, 2012. "The Prognostic Role of RASSF1A Promoter Methylation in Breast Cancer: A Meta-Analysis of Published Data," PLOS ONE, Public Library of Science, vol. 7(5), pages 1-7, May.
  • Handle: RePEc:plo:pone00:0036780
    DOI: 10.1371/journal.pone.0036780
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    Cited by:

    1. Di Liu & Hongli Peng & Qi Sun & Zhongyao Zhao & Xinwei Yu & Siqi Ge & Hao Wang & Honghong Fang & Qing Gao & Jiaonan Liu & Lijuan Wu & Manshu Song & Youxin Wang, 2017. "The Indirect Efficacy Comparison of DNA Methylation in Sputum for Early Screening and Auxiliary Detection of Lung Cancer: A Meta-Analysis," IJERPH, MDPI, vol. 14(7), pages 1-14, June.
    2. Chihao Shao & Wenzhu Dai & Haili Li & Wenru Tang & Shuting Jia & Xiaoming Wu & Ying Luo, 2017. "The relationship between RASSF1A gene promoter methylation and the susceptibility and prognosis of melanoma: A meta-analysis and bioinformatics," PLOS ONE, Public Library of Science, vol. 12(2), pages 1-12, February.

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