FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer

Partha S. Ray; Jinhua Wang; Ying Qu; Myung Shin Sim; Jaime Shamonki; Sanjay P. Bagaria; Xing Ye; Bingya Liu; David Elashoff; Dave S. Hoon; Michael A. Walter; John W. Martens; Andrea L. Richardson; Armando E. Giuliano; Xiaojiang Cui

doi:10.1158/0008-5472.CAN-09-4120

FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer

Partha S. Ray, Jinhua Wang, Ying Qu, Myung Shin Sim, Jaime Shamonki, Sanjay P. Bagaria, Xing Ye, Bingya Liu, David Elashoff, Dave S. Hoon, Michael A. Walter, John W. Martens, Andrea L. Richardson, Armando E. Giuliano, Xiaojiang Cui

Research output: Contribution to journal › Article › peer-review

172 Scopus citations

Abstract

Gene expression signatures for a basal-like breast cancer (BLBC) subtype have been associated with poor clinical outcomes, but a molecular basis for this disease remains unclear. Here, we report overexpression of the transcription factor FOXC1 as a consistent feature of BLBC compared with other molecular subtypes of breast cancer. Elevated FOXC1 expression predicted poor overall survival in BLBC (P = 0.0001), independently of other clinicopathologic prognostic factors including lymph node status, along with a higher incidence of brain metastasis (P = 0.02) and a shorter brain metastasis-free survival in lymph node-negative patients (P < 0.0001). Ectopic overexpression of FOXC1 in breast cancer cells increased cell proliferation, migration, and invasion, whereas shRNA-mediated FOXC1 knockdown yielded opposite effects. Our findings identify FOXC1 as a theranostic biomarker that is specific for BLBC, offering not only a potential prognostic candidate but also a potential molecular therapeutic target in this breast cancer subtype.

Original language	English (US)
Pages (from-to)	3870-3876
Number of pages	7
Journal	Cancer Research
Volume	70
Issue number	10
DOIs	https://doi.org/10.1158/0008-5472.CAN-09-4120
State	Published - May 15 2010
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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Ray, P. S., Wang, J., Qu, Y., Sim, M. S., Shamonki, J., Bagaria, S. P., Ye, X., Liu, B., Elashoff, D., Hoon, D. S., Walter, M. A., Martens, J. W., Richardson, A. L., Giuliano, A. E., & Cui, X. (2010). FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer. Cancer Research, 70(10), 3870-3876. https://doi.org/10.1158/0008-5472.CAN-09-4120

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abstract = "Gene expression signatures for a basal-like breast cancer (BLBC) subtype have been associated with poor clinical outcomes, but a molecular basis for this disease remains unclear. Here, we report overexpression of the transcription factor FOXC1 as a consistent feature of BLBC compared with other molecular subtypes of breast cancer. Elevated FOXC1 expression predicted poor overall survival in BLBC (P = 0.0001), independently of other clinicopathologic prognostic factors including lymph node status, along with a higher incidence of brain metastasis (P = 0.02) and a shorter brain metastasis-free survival in lymph node-negative patients (P < 0.0001). Ectopic overexpression of FOXC1 in breast cancer cells increased cell proliferation, migration, and invasion, whereas shRNA-mediated FOXC1 knockdown yielded opposite effects. Our findings identify FOXC1 as a theranostic biomarker that is specific for BLBC, offering not only a potential prognostic candidate but also a potential molecular therapeutic target in this breast cancer subtype.",

author = "Ray, {Partha S.} and Jinhua Wang and Ying Qu and Sim, {Myung Shin} and Jaime Shamonki and Bagaria, {Sanjay P.} and Xing Ye and Bingya Liu and David Elashoff and Hoon, {Dave S.} and Walter, {Michael A.} and Martens, {John W.} and Richardson, {Andrea L.} and Giuliano, {Armando E.} and Xiaojiang Cui",

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AU - Shamonki, Jaime

AU - Bagaria, Sanjay P.

AU - Ye, Xing

AU - Liu, Bingya

AU - Elashoff, David

AU - Hoon, Dave S.

AU - Walter, Michael A.

AU - Martens, John W.

AU - Richardson, Andrea L.

AU - Giuliano, Armando E.

AU - Cui, Xiaojiang

PY - 2010/5/15

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N2 - Gene expression signatures for a basal-like breast cancer (BLBC) subtype have been associated with poor clinical outcomes, but a molecular basis for this disease remains unclear. Here, we report overexpression of the transcription factor FOXC1 as a consistent feature of BLBC compared with other molecular subtypes of breast cancer. Elevated FOXC1 expression predicted poor overall survival in BLBC (P = 0.0001), independently of other clinicopathologic prognostic factors including lymph node status, along with a higher incidence of brain metastasis (P = 0.02) and a shorter brain metastasis-free survival in lymph node-negative patients (P < 0.0001). Ectopic overexpression of FOXC1 in breast cancer cells increased cell proliferation, migration, and invasion, whereas shRNA-mediated FOXC1 knockdown yielded opposite effects. Our findings identify FOXC1 as a theranostic biomarker that is specific for BLBC, offering not only a potential prognostic candidate but also a potential molecular therapeutic target in this breast cancer subtype.

AB - Gene expression signatures for a basal-like breast cancer (BLBC) subtype have been associated with poor clinical outcomes, but a molecular basis for this disease remains unclear. Here, we report overexpression of the transcription factor FOXC1 as a consistent feature of BLBC compared with other molecular subtypes of breast cancer. Elevated FOXC1 expression predicted poor overall survival in BLBC (P = 0.0001), independently of other clinicopathologic prognostic factors including lymph node status, along with a higher incidence of brain metastasis (P = 0.02) and a shorter brain metastasis-free survival in lymph node-negative patients (P < 0.0001). Ectopic overexpression of FOXC1 in breast cancer cells increased cell proliferation, migration, and invasion, whereas shRNA-mediated FOXC1 knockdown yielded opposite effects. Our findings identify FOXC1 as a theranostic biomarker that is specific for BLBC, offering not only a potential prognostic candidate but also a potential molecular therapeutic target in this breast cancer subtype.

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FOXC1 is a potential prognostic biomarker with functional significance in basal-like breast cancer

Abstract

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