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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.


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pone.0136374.g001: Meta-analysis flow chart.

Mentions: A literature search of PubMed, EMBASE, the Cochrane Library and the annual meetings of ESMO and ASCO yielded 184 articles. After reviewing the titles and abstracts of these 184 articles, 140 articles were excluded by the inclusion criteria established for this study (see the Materials and Methods). Among the remaining articles whose full text was reviewed, 28 were excluded due to duplication, a lack of sufficient data, irrelevance to the prognostic value of FOXP3, or non-operable breast cancer. As a result, 16 publications were finally selected for a meta-analysis of the prognostic value of FOXP3 in BC (Fig 1). The detailed included and excluded studies are available in the S2 File. These publications provided data from a total of 13,217 patients who presented with BC, and the sample sizes ranged from 90 to 3,276 participants. Only Ali et al. [7] used data from previous studies conducted by Liu et al. [6], Mahmoud et al. [27], and other studies [28, 29]. Furthermore, among the 16 selected publications, DFS data were extracted from 9 of the articles, OS data were extracted from 14 of the articles, and clinicopathological parameters data were extracted from 8 of the articles. The details of the 16 included publications are summarized in Table 2. All of the data, except that from the study by Kim et al. [8], were used for univariate analysis. FOXP3 was expressed in intratumoral lymphocytes, peritumoral lymphocytes, and/or tumor cells. The FOXP3-positive cut-off values were based on either the median or on other values. The NOS scores of these studies ranged from 4 to 7 (with a mean of 5.38) (Table 2 and S1 Table), demonstrating that the quality of the included studies was acceptable.


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)

Meta-analysis flow chart.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0136374.g001: Meta-analysis flow chart.
Mentions: A literature search of PubMed, EMBASE, the Cochrane Library and the annual meetings of ESMO and ASCO yielded 184 articles. After reviewing the titles and abstracts of these 184 articles, 140 articles were excluded by the inclusion criteria established for this study (see the Materials and Methods). Among the remaining articles whose full text was reviewed, 28 were excluded due to duplication, a lack of sufficient data, irrelevance to the prognostic value of FOXP3, or non-operable breast cancer. As a result, 16 publications were finally selected for a meta-analysis of the prognostic value of FOXP3 in BC (Fig 1). The detailed included and excluded studies are available in the S2 File. These publications provided data from a total of 13,217 patients who presented with BC, and the sample sizes ranged from 90 to 3,276 participants. Only Ali et al. [7] used data from previous studies conducted by Liu et al. [6], Mahmoud et al. [27], and other studies [28, 29]. Furthermore, among the 16 selected publications, DFS data were extracted from 9 of the articles, OS data were extracted from 14 of the articles, and clinicopathological parameters data were extracted from 8 of the articles. The details of the 16 included publications are summarized in Table 2. All of the data, except that from the study by Kim et al. [8], were used for univariate analysis. FOXP3 was expressed in intratumoral lymphocytes, peritumoral lymphocytes, and/or tumor cells. The FOXP3-positive cut-off values were based on either the median or on other values. The NOS scores of these studies ranged from 4 to 7 (with a mean of 5.38) (Table 2 and S1 Table), demonstrating that the quality of the included studies was acceptable.

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