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Meta-Analysis
. 2017 Jun 6;116(12):1585-1594.
doi: 10.1038/bjc.2017.130. Epub 2017 May 16.

BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses

E S Papadakis  1 , T Reeves  1 , N H Robson  1 , T Maishman  2 , G Packham  1 , R I Cutress  1   3
Affiliations
Meta-Analysis

BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses

E S Papadakis et al. Br J Cancer. .

Abstract

Background: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer.

Methods: A systematic review of published studies reporting BAG-1 (mRNA and/or protein) expression and clinical outcome in early breast cancer. The REporting Recommendations for Tumour MARKer and Prognostic Studies (REMARK) criteria were used as a template against which data were assessed. Meta-analyses were performed for studies that provided a hazard ratio and 95% confidence intervals for clinical outcomes including disease-free survival or breast cancer-specific survival from univariate analysis.

Results: Eighteen studies used differing methodologies and reported on differing outcomes. Meta-analyses were only possible on results from a subset of reported studies. Meta-analyses suggested improved outcome with high BAG-1 mRNA and high BAG-1 nuclear expression by immunohistochemisty.

Conclusions: Increased levels of BAG-1 are associated with better breast cancer outcomes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart illustrating the selection methodology for eligible studies.
Figure 2
Figure 2
Meta-analyses of: (A) BAG-1 mRNA (high v low) for BCSS. Data for van de Vijver et al., and Nadieri et al., are from analyses published in Millar et al (2009), and for Curtis et al., are from analyisis included in Papadakis et al., and 95% CI obtained from the authors of Papadakis et al (2016) (B) nuclear BAG-1 protein by immunohistochemistry (high v low) for BCSS; and (C) nuclear BAG-1 protein by immunohistochemistry (high v low) for DDFS.
See this image and copyright information in PMC

Comment in

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