FOXC2 is a novel prognostic factor in human esophageal squamous cell carcinoma.
BACKGROUND
FOXC2 has been implicated in cancer progression through its induction of epithelial-to-mesenchymal transition. We analyzed the clinical significance of FOXC2 in esophageal cancer cases, in which early distant metastasis or invasion to nearby organs is an obstacle to treatment.


METHODS
Quantitative reverse transcriptase-polymerase chain reaction was used to evaluate FOXC2 mRNA expression in 70 esophageal cancer cases to determine the clinicopathologic significance of FOXC2 expression. Furthermore, we examined associations between FOXC2 expression and matrix metalloproteinases 2 (MMP2) and matrix metalloproteinases 9 (MMP9). We also performed in vitro invasion and migration assays for FOXC2-suppressed esophageal cancer cells.


RESULTS
In clinicopathologic analysis, the high-FOXC2 expression group showed a higher incidence of advanced tumor stage, lymph node metastasis, and lymphatic invasion than the low-FOXC2 expression group (P < 0.05). In particular, tumor stage exhibited the most remarkable difference (P < 0.0001). Expression of MMP2 and MMP9 was far higher in the high-FOXC2 expression group. Furthermore, the high-FOXC2 expression group had a significantly poorer prognosis than did the low expression group (P = 0.006). Multivariate analysis indicated that high FOXC2 expression was an independent prognostic factor for survival. Suppression of FOXC2 expression altered the invasive and the migratory ability of esophageal cancer cells in vitro.


CONCLUSIONS
Our findings suggest that FOXC2 could be an important prognostic indicator for esophageal cancer patients. FOXC2 is directly involved in cancer progression and is associated with poor prognosis in esophageal cancer cases.
Nishida
Naohiro
N
Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Oita, Japan.
Mimori
Koshi
K
Yokobori
Takehiko
T
Sudo
Tomoya
T
Tanaka
Fumiaki
F
Shibata
Kohei
K
Ishii
Hideshi
H
Doki
Yuichiro
Y
Mori
Masaki
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; C082078:mesenchyme fork head 1 protein; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9