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FOXC2 Expression is Associated with Tumor Proliferation and Invasion Potential in Oral Tongue Squamous Cell Carcinoma

Pathology & Oncology Research volume 21, pages 783–791 (2015)Cite this article

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.

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Abbreviations

OSCC:

Oral squamous cell carcinoma

FOXC2:

Forkhead box protein C2

OTSCC:

Oral tongue squamous cell carcinoma

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This study was supported in part by Grant 24792236 from the Ministry of Education, Culture, Sports, Science and Technology, Japan for S. Yamada.

Conflict of Interests

None.

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Affiliations

  1. 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

    Naomi Imayama, Shin-ichi Yamada, Souichi Yanamoto, Tomofumi Naruse, Yuki Matsushita, Hidenori Takahashi & Masahiro Umeda

  2. Department of Oral Pathology and Bone Metabolism, Unit of Basic Medical Sciences, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Sachiko Seki, Shuichi Fujita & Tohru Ikeda

Authors
  1. Naomi Imayama
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  2. Shin-ichi Yamada
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  3. Souichi Yanamoto
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  4. Tomofumi Naruse
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  5. Yuki Matsushita
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  7. Sachiko Seki
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  8. Shuichi Fujita
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  9. Tohru Ikeda
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  10. Masahiro Umeda
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Correspondence to Shin-ichi Yamada.

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Imayama, N., Yamada, Si., Yanamoto, S. et al. FOXC2 Expression is Associated with Tumor Proliferation and Invasion Potential in Oral Tongue Squamous Cell Carcinoma. Pathol. Oncol. Res. 21, 783–791 (2015). https://doi.org/10.1007/s12253-014-9891-6

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  • DOI: https://doi.org/10.1007/s12253-014-9891-6

Keywords

  • FOXC2
  • Invasion
  • Metastasis
  • Proliferation
  • Oral tongue squamous cell carcinoma