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The Prognostic Value of Forkhead Box P3 Expression in Operable Breast Cancer: A Large-Scale Meta-Analysis

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  • Shu Chen Lin
  • Zhi Hua Gan
  • Yang Yao
  • Da Liu Min

Abstract

Background: Recent studies have shown that the forkhead box P3 (FOXP3) protein has a prognostic role in breast cancer. However, these results are controversial. Therefore, the aim of this meta-analysis was to clarify the prognostic role of FOXP3 expression in operable breast cancer cases. Methods: Eligible studies describing the use of FOXP3 as a prognostic factor for operable breast cancer cases were identified. Clinicopathological features, disease-free survival (DFS), and overall survival (OS) data were collected from these studies and were analyzed using Stata software. Results: A total of 16 articles containing data from 13,217 breast cancer patients met the inclusion criteria established for this study. The subsequent meta-analysis that was performed showed that high levels of FOXP3 are not significantly associated with DFS and OS with significant heterogeneity. An additional subgroup analysis demonstrated that intratumoral FOXP3+ regulatory T cells (Tregs) were positively correlated with adverse clinicopathological parameters, yet they did not show an association with DFS or OS. For tumor cells, the pooled results revealed that FOXP3 is significantly associated with DFS (HR: 2.55, 95% CI: 1.23–5.30) but is not associated with clinicopathological parameters or OS. We also observed a significant correlation between FOXP3 expression and survival in the estrogen receptor-positive (ER)+ subgroup (HR: 1.83, 95% CI: 1.36–2.47 for DFS, HR: 1.87, 95% CI 1.28–2.73 for OS), in the Asian region (HR: 1.98, 95% CI: 1.56–2.50 for DFS, HR: 1.93, 95% CI: 1.12–3.35 for OS) and using the median as the FOXP3-positive cut-off value (HR: 1.94, 95% CI: 1.57–2.39 for DFS, HR: 2.06; 95% CI: 1.36–3.11 for OS). Conclusion: This meta-analysis indicates that a prognostic role for FOXP3 expression in operable breast cancer cases depends on the FOXP3-positive region, ER status, geographic region and the FOXP3-positive cut-off value.

Suggested Citation

  • Shu Chen Lin & Zhi Hua Gan & Yang Yao & Da Liu Min, 2015. "The Prognostic Value of Forkhead Box P3 Expression in Operable Breast Cancer: A Large-Scale Meta-Analysis," PLOS ONE, Public Library of Science, vol. 10(8), pages 1-17, August.
  • Handle: RePEc:plo:pone00:0136374
    DOI: 10.1371/journal.pone.0136374
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    1. Sue Duval & Richard Tweedie, 2000. "Trim and Fill: A Simple Funnel-Plot–Based Method of Testing and Adjusting for Publication Bias in Meta-Analysis," Biometrics, The International Biometric Society, vol. 56(2), pages 455-463, June.
    2. Kim, Jaehoon & Kim, Sangsin, 2015. "2012년 국회법 개정의 효과 연구 [A Study on the Effect of the 2012 National Assembly Act Amendment]," KDI Research Monographs, Korea Development Institute (KDI), volume 127, number v:2015-03(k):y:2015:p:1-1.
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    1. Jian Xiao & Yong Zou & Xi Chen & Ying Gao & Mingxuan Xie & Xiaoxiao Lu & Wei Li & Bixiu He & Shuya He & Shaojin You & Qiong Chen, 2016. "The Prognostic Value of Decreased LKB1 in Solid Tumors: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 11(4), pages 1-14, April.

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