Authors' Affiliations: Departments of Surgical Oncology, Molecular Oncology, and Biostatistics, John Wayne Cancer Institute; Department of Pathology, St. John's Health Center, Santa Monica, California; Department of Surgery, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China; Division of General Internal Medicine, School of Medicine, University of California at Los Angeles, Los Angeles, California; Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada; Department of Medical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands; and Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Cancer Res. 2010 Apr 20.
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. Cancer Res; 70(10); OF1-7. (c)2010 AACR.
PMID: 20406990 [PubMed - as supplied by publisher] Source: National Library of Medicine.
