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

Lin SC, Gan ZH, Yao Y, Min da L - PLoS ONE (2015)

Bottom Line: However, these results are controversial.The subsequent meta-analysis that was performed showed that high levels of FOXP3 are not significantly associated with DFS and OS with significant heterogeneity.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Shanghai Sixth People's Hospital East Campus, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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pone.0136374.g007: 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.

Mentions: For DFS, the shape of the funnel plots appeared asymmetrical, which might indicate a publication bias. However, Begg’s and Egger’s tests showed a statistically non-significant value (P = 1.000 and 0.362, respectively) (Fig 6A). Then we conducted sensitivity analysis using the trim and fill method. After imputing two hypothetical studies, the funnel plots become symmetrical (Fig 6B) and the pooled analysis did not change significantly (HR: 1.29, 95% CI: 0.90–1.84). With respect to the OS, no evidence for asymmetry was observed in the funnel plots, and Begg’s and Egger’s tests also revealed no evidence of publication bias (P = 0.822 and 0.658, respectively) (Fig 7A). Moreover, the trim and fill method showed that the theoretical missing studies didn’t exist (Fig 7B).


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

Lin SC, Gan ZH, Yao Y, Min da L - PLoS ONE (2015)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549287&req=5

pone.0136374.g007: 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.
Mentions: For DFS, the shape of the funnel plots appeared asymmetrical, which might indicate a publication bias. However, Begg’s and Egger’s tests showed a statistically non-significant value (P = 1.000 and 0.362, respectively) (Fig 6A). Then we conducted sensitivity analysis using the trim and fill method. After imputing two hypothetical studies, the funnel plots become symmetrical (Fig 6B) and the pooled analysis did not change significantly (HR: 1.29, 95% CI: 0.90–1.84). With respect to the OS, no evidence for asymmetry was observed in the funnel plots, and Begg’s and Egger’s tests also revealed no evidence of publication bias (P = 0.822 and 0.658, respectively) (Fig 7A). Moreover, the trim and fill method showed that the theoretical missing studies didn’t exist (Fig 7B).

Bottom Line: However, these results are controversial.The subsequent meta-analysis that was performed showed that high levels of FOXP3 are not significantly associated with DFS and OS with significant heterogeneity.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Shanghai Sixth People's Hospital East Campus, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

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.

No MeSH data available.


Related in: MedlinePlus