title: FOXC2 expression is associated with tumor proliferation and invasion potential in oral tongue squamous cell carcinoma.
abstract: Forkhead box protein C2 (FOXC2) is a gene encoding a transcription factor that controls the generation of mesodermal tissue including vascular and lymphatic tissues. FOXC2 has previously been associated with EMT and tumor angiogenesis in various cancers. Moreover, a relationship between the expression of FOXC2 and poor prognosis has been reported in various cancers. We herein examined the clinicopathological significance of FOXC2 in oral tongue squamous cell carcinoma (OTSCC) and attempted to clarify the function of FOXC2 in OTSCC cell lines in vitro. The overexpression of FOXC2 was more frequent in cancers with higher grades according to the pattern of invasion (grade 4 vs. 1-3; p < 0.05). A correlation was observed between the expression of FOXC2 and that of VEGF-A and -C (VEGF-A; p < 0.05, VEGF-C; p < 0.001). The high-FOXC2 expression group had a significantly poorer prognosis than that of the low-expression group (p < 0.001). Multivariate analysis indicated that the overexpression of FOXC2 may also be an independent prognostic factor, similar to N classification (N0 vs 1/2; p < 0.05), stage classification (stage I/II vs III/IV; p < 0.05), pattern of invasion (grade 1-3vs 4; p < 0.05), local recurrence (local recurrence (+) vs (-); p < 0.01), and the overexpression of FOXC2 (FOXC2 overexpression (-) vs.(+); p < 0.05). In the OTSCC cell line analysis, the expression of FOXC2 was also associated with proliferation and invasion potential. These results strongly suggest that the overexpression of FOXC2 may be a potent predictor of survival in OTSCC patients.
authors.affiliation: Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Imayama
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Souichi
authors.initials: S
authors.lastname: Yanamoto
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Naruse
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Seki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Fujita
authors.forename: Tohru
authors.initials: T
authors.lastname: Ikeda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umeda
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; C082078:mesenchyme fork head 1 protein