Expression of the BAD Pathway is a Marker of Triple-negative Status and Poor Outcome

Overview

Journal Sci Rep

Specialty Science

Date 2019 Nov 27

PMID 31767884

Citations 9

Authors

Bernadette M Boac

Forough Abbasi

Roohi Ismail-Khan

Yin Xiong

Atif Siddique

Hannah Park

Mingda Han

Daryoush Saeed-Vafa

Hatem Soliman

Brendon Henry

M Juliana Pena

E Clair McClung

Sharon E Robertson

Sarah L Todd

Alex Lopez

Weihong Sun

Susmitha Apuri

Johnathan M Lancaster

Anders E Berglund

Anthony M Magliocco

Douglas C Marchion

Affiliations

Soon will be listed here.

Abstract

Triple-negative breast cancer (TNBC) has few therapeutic targets, making nonspecific chemotherapy the main treatment. Therapies enhancing cancer cell sensitivity to cytotoxic agents could significantly improve patient outcomes. A BCL2-associated agonist of cell death (BAD) pathway gene expression signature (BPGES) was derived using principal component analysis (PCA) and evaluated for associations with the TNBC phenotype and clinical outcomes. Immunohistochemistry was used to determine the relative expression levels of phospho-BAD isoforms in tumour samples. Cell survival assays evaluated the effects of BAD pathway inhibition on chemo-sensitivity. BPGES score was associated with TNBC status and overall survival (OS) in breast cancer samples of the Moffitt Total Cancer Care dataset and The Cancer Genome Atlas (TCGA). TNBC tumours were enriched for the expression of phospho-BAD isoforms. Further, the BPGES was associated with TNBC status in breast cancer cell lines of the Cancer Cell Line Encyclopedia (CCLE). Targeted inhibition of kinases known to phosphorylate BAD protein resulted in increased sensitivity to platinum agents in TNBC cell lines compared to non-TNBC cell lines. The BAD pathway is associated with triple-negative status and OS. TNBC tumours were enriched for the expression of phosphorylated BAD protein compared to non-TNBC tumours. These findings suggest that the BAD pathway it is an important determinant of TNBC clinical outcomes.

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