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

Annals of Surgical Oncology volume 18, pages 535–542 (2011)Cite this article

Abstract

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.

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Acknowledgment

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.

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Affiliations

  1. Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Oita, Japan

    Naohiro Nishida MD, Koshi Mimori MD, Takehiko Yokobori MD, Tomoya Sudo MD, Fumiaki Tanaka MD, Kohei Shibata MD & Masaki Mori MD, FACS

  2. Department of Surgical Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan

    Naohiro Nishida MD, Hideshi Ishii MD, Yuichiro Doki MD & Masaki Mori MD, FACS

Authors
  1. Naohiro Nishida MD
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  2. Koshi Mimori MD
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  3. Takehiko Yokobori MD
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  4. Tomoya Sudo MD
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  5. Fumiaki Tanaka MD
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  6. Kohei Shibata MD
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  7. Hideshi Ishii MD
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  8. Yuichiro Doki MD
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  9. Masaki Mori MD, FACS
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Corresponding author

Correspondence to Masaki Mori MD, FACS.

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Nishida, N., Mimori, K., Yokobori, T. et al. FOXC2 is a Novel Prognostic Factor in Human Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 18, 535–542 (2011). https://doi.org/10.1245/s10434-010-1274-y

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  • DOI: https://doi.org/10.1245/s10434-010-1274-y

Keywords

  • Esophageal Cancer
  • Esophageal Squamous Cell Carcinoma
  • Lymphatic Invasion
  • Esophageal Cancer Patient
  • Esophageal Cancer Cell