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

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. BAG-1 exists as multiple protein isoforms which 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 specifcally 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 REMARK criteria were used as a template against which data was assessed. Meta-analyses was performed for studies that provided a hazard ratio (HR) and 95% confidence intervals (CIs) for clincal outcomes including disease free survival (DFS) or breast cancer specific survival (BCSS) from univariate analysis.

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

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

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