Annals of Surgical Oncology

, Volume 18, Issue 2, pp 535–542 | Cite as

FOXC2 is a Novel Prognostic Factor in Human Esophageal Squamous Cell Carcinoma

  • Naohiro Nishida
  • Koshi Mimori
  • Takehiko Yokobori
  • Tomoya Sudo
  • Fumiaki Tanaka
  • Kohei Shibata
  • Hideshi Ishii
  • Yuichiro Doki
  • Masaki Mori
Thoracic Oncology



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.


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.


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.


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.


Esophageal Cancer Esophageal Squamous Cell Carcinoma Lymphatic Invasion Esophageal Cancer Patient Esophageal Cancer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank T. Shimooka, K. Ogata, M. Kasagi, and T. Kawano for their excellent technical assistance. This work was supported in part by the following grants and foundations: CREST, Japan Science and Technology Agency (JST); Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research: 21679006, 20390360, 20590313, 20591547, 21591644, 21592014, 20790960, 21791297, 21229015, 20659209 and 20012039; NEDO (New Energy and Industrial Technology Development Organization) Technological Development for Chromosome Analysis; The Ministry of Education, Culture, Sports, Science and Technology of Japan for Scientific Research on Priority Areas, Cancer Translational Research Project, Japan.

Conflict of interest



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Copyright information

© Society of Surgical Oncology 2010

Authors and Affiliations

  • Naohiro Nishida
    • 1
    • 2
  • Koshi Mimori
    • 1
  • Takehiko Yokobori
    • 1
  • Tomoya Sudo
    • 1
  • Fumiaki Tanaka
    • 1
  • Kohei Shibata
    • 1
  • Hideshi Ishii
    • 2
  • Yuichiro Doki
    • 2
  • Masaki Mori
    • 1
    • 2
  1. 1.Department of Surgery and Molecular Oncology, Medical Institute of BioregulationKyushu UniversityBeppuJapan
  2. 2.Department of Surgical Oncology, Graduate School of MedicineOsaka UniversityOsakaJapan

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