BAG-1 may predict survival in early breast cancer patients
The co-chaperone protein B-cell lymphoma 2 (Bcl-2)-associated athanogene-1 (BAG-1) demonstrates prognostic value in early breast cancer, such that increased expression of BAG-1 mRNA and protein is associated with better outcomes, according to a systematic review and meta-analysis.
The analysis included 18 studies assessing the clinical significance of BAG-1 as a prognostic marker in breast cancer patients. BAG-1 mRNA expression was evaluated by methods including reverse transcription polymerase chain reaction (RT-PCR; two studies) and immunohistochemical staining (15 studies). Majority used full-face sections from formalin-fixed paraffin-embedded (FFPE) tumours (11 studies), whereas the remaining seven utilised FFPE tissue microarrays. [Br J Cancer 2017;116:1585–1594]
While data were too heterogeneous and outcome measures too varied to pool the results for majority of the studies, meta-analyses of mRNA expression from two studies involving a total of 2,422 patients yielded a hazard ratio (HR) of 0.55 (95 percent CI, 0.36 to 0.85), favouring improved breast cancer-specific survival (BCSS) with high expression of BAG-1.
Similarly, two studies involving 336 patients and evaluating pathologist assessment of nuclear BAG-1 found BCSS to improve with high BAG-1 levels (HR, 0.36; 0.23 to 0.55).
Finally, two studies that included 1,239 patients and investigated nuclear BAG-1 and distant disease-free survival reported improved outcomes with high BAG-1 expression (HR, 0.70; 0.59 to 0.84).
“The concept that BAG-1, a protein that supports cancer cell survival, is related to improved patient survival may seem paradoxical. This observation, however, is not without precedent as both the [oestrogen receptor (ER)] and Bcl-2, another antiapoptotic protein, [are] also associated with good prognosis in breast cancer,” the authors said, noting the increasing evidence supporting the hypothesis that BAG-1 plays an important role in breast cancer.
“The development of high-throughput assays, such as oncotype DX and PAM50, reveal that increased BAG-1 mRNA is associated with a low risk of recurrence and improved prognosis. In addition, a large RT-PCR study of a clinical trial cohort is also consistent with this,” they said. [Clin Cancer Res 2015;21:2763–2770]
The authors also cited recent data demonstrating that high nuclear BAG-1 immunoreactivity is an independent predictor of outcome, particularly in patients with ER+ early breast cancer receiving adjuvant hormonal therapy, and enhances the predictive power of IH4 staining. “Including BAG-1 immunohistochemical staining as a standard biomarker in the clinic may therefore help to better stratify patients according to their risk of disease recurrence and determine their probability of responding to therapy.”
They explained that the influence of BAG-1 on patient survival may be partly explained by the regulation of ER function, particularly at an early stage of the disease. [Cell Physiol Biochem 2014;33:365–374]
While the findings might be limited by the heterogeneity between studies, resulting in a considerable number of studies that could not be included in the analysis, the authors said the present review and meta-analyses “suggest that increased expression of BAG-1 mRNA and BAG-1 protein, and in particular nuclear expression, appears to be associated with improved breast cancer outcomes.”