title: 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.affiliation: Department of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
authors.forename: Partha S
authors.initials: PS
authors.lastname: Ray
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.forename: Myung-Shin
authors.initials: MS
authors.lastname: Sim
authors.forename: Jaime
authors.initials: J
authors.lastname: Shamonki
authors.forename: Sanjay P
authors.initials: SP
authors.lastname: Bagaria
authors.forename: Xing
authors.initials: X
authors.lastname: Ye
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Dave S
authors.initials: DS
authors.lastname: Hoon
authors.forename: Michael A
authors.initials: MA
authors.lastname: Walter
authors.forename: John W
authors.initials: JW
authors.lastname: Martens
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Richardson
authors.forename: Armando E
authors.initials: AE
authors.lastname: Giuliano
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Cui
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering