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Meta-Analysis
. 2015 Aug 25;10(8):e0136374.
doi: 10.1371/journal.pone.0136374. eCollection 2015.

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

Shu Chen Lin  1 , Zhi Hua Gan  1 , Yang Yao  2 , Da Liu Min  1
Affiliations
Meta-Analysis

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

Shu Chen Lin et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Meta-analysis flow chart.
Fig 2
Fig 2. FOXP3 expression and DFS.
Fig 3
Fig 3. Sensitivity analysis of DFS in the meta-analysis.
Fig 4
Fig 4. FOXP3 expression and OS.
Fig 5
Fig 5. Sensitivity analysis of OS in the meta-analysis.
Fig 6
Fig 6. Funnel plots in the context of DFS without and with trim and fill.
The pseudo 95% CI is computed as part of the analysis that produces the funnel plot, and corresponds to the expected 95% CI for a given SE.
Fig 7
Fig 7. Funnel plots in the context of OS without and with trim and fill.
The pseudo 95% CI is computed as part of the analysis that produces the funnel plot, and corresponds to the expected 95% CI for a given SE.
See this image and copyright information in PMC

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