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

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.

• Authors: 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
• Journal: Cancer research (Cancer Res) Vol. 70 Issue 10 Pg. 3870-6 (May 15 2010) ISSN: 1538-7445 [Electronic] United States
• PMID: 20406990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c)2010 AACR.

Chemical References

• Biomarkers, Tumor
• FOXC1 protein, human
• Forkhead Transcription Factors
• RNA, Messenger
• RNA, Small Interfering

Topics

• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Blotting, Western
• Bone Neoplasms (genetics, metabolism, secondary)
• Breast (metabolism, pathology)
• Breast Neoplasms (genetics, metabolism, pathology)
• Carcinoma, Basal Cell (genetics, metabolism, pathology)
• Cell Adhesion
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Female
• Forkhead Transcription Factors (antagonists & inhibitors, genetics, metabolism)
• Gene Expression Profiling
• Humans
• Oligonucleotide Array Sequence Analysis
• Prognosis
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Rate