Expression of the BAD pathway is a marker of triple-negative status and poor outcome

被引：18

作者：

Boac, Bernadette M. ^{[1
,2
]}

Abbasi, Forough ^{[3
]}

Ismail-Khan, Roohi ^{[4
,5
]}

Xiong, Yin ^{[1
,2
]}

Siddique, Atif ^{[1
]}

Park, Hannah ^{[1
,2
]}

Han, Mingda ^{[1
,2
]}

Saeed-Vafa, Daryoush ^{[1
]}

Soliman, Hatem ^{[4
,5
]}

Henry, Brendon ^{[1
]}

Pena, M. Juliana ^{[1
]}

McClung, E. Clair ^{[6
]}

Robertson, Sharon E. ^{[7
]}

Todd, Sarah L. ^{[5
]}

Lopez, Alex ^{[1
]}

Sun, Weihong ^{[5
]}

Apuri, Susmitha ^{[5
]}

Lancaster, Johnathan M. ^{[8
]}

Berglund, Anders E. ^{[9
]}

Magliocco, Anthony M. ^{[10
]}

Marchion, Douglas C. ^{[1
,2
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Anat Pathol, Tampa, FL 33612 USA

[2] H Lee Moffitt Canc Ctr & Res Inst, Chem Biol & Mol Med, Tampa, FL 33612 USA

[3] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[4] H Lee Moffitt Canc Ctr & Res Inst, Dept Oncol Sci, Tampa, FL 33612 USA

[5] H Lee Moffitt Canc Ctr & Res Inst, Dept Womens Oncol, Tampa, FL 33612 USA

[6] Univ Arizona, Canc Ctr, Obstet & Gynecol, Tucson, AZ 85724 USA

[7] Indiana Univ Hlth, Indianapolis, IN 46202 USA

[8] Myriad Genet, Salt Lake City, UT 84108 USA

[9] H Lee Moffitt Canc Ctr & Res Inst, Dept Bioinformat & Biostat, Tampa, FL 33612 USA

[10] Protean Diagnost, Tampa, FL 33612 USA

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

基金：

美国国家卫生研究院;

关键词：

DEPENDENT PROTEIN-KINASE; CYTOCHROME-C RELEASE; BREAST-CANCER; CELL-DEATH; OVARIAN-CANCER; BCL2; ANTAGONIST; BH3; DOMAIN; BASAL-LIKE; PHOSPHORYLATION; APOPTOSIS;

D O I：

10.1038/s41598-019-53695-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

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