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. 2018 May 25;18(1):597.
doi: 10.1186/s12885-018-4503-6.

High expression of forkhead box protein C2 is associated with aggressive phenotypes and poor prognosis in clinical hepatocellular carcinoma

Yuki Shimoda  1 , Yasunari Ubukata  2 , Tadashi Handa  1 , Takehiko Yokobori  3 , Takayoshi Watanabe  2 , Dolgormaa Gantumur  2 , Kei Hagiwara  2 , Takahiro Yamanaka  2 , Mariko Tsukagoshi  2 , Takamichi Igarashi  2 , Akira Watanabe  2 , Norio Kubo  2 , Kenichiro Araki  2 , Norifumi Harimoto  2 , Ayaka Katayama  1 , Toshiaki Hikino  1 , Takaaki Sano  1 , Kyoichi Ogata  2 , Hiroyuki Kuwano  2 , Ken Shirabe  2 , Tetsunari Oyama  1
Affiliations

High expression of forkhead box protein C2 is associated with aggressive phenotypes and poor prognosis in clinical hepatocellular carcinoma

Yuki Shimoda et al. BMC Cancer. .

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the major causes of tumor death; thus, the identification of markers related to its diagnosis and prognosis is critical. Previous studies have revealed that epithelial-to-mesenchymal transition (EMT) is involved in tumor invasion and metastasis, and the forkhead box protein C2 (FOXC2) has been shown to promote tumor cell proliferation, invasion, and EMT. In the present study, we examined the clinicopathological significance of FOXC2 and EMT-related markers in clinical HCC specimens and identified factors related to the diagnosis and prognosis of HCC.

Methods: The expression of FOXC2 and EMT-related markers was evaluated by immunohistochemistry in 84 cases of hepatocellular carcinoma.

Results: A high expression of FOXC2 was observed in 26 of 84 cases, and expression was significantly correlated with background liver cirrhosis, poor tumor differentiation, high serum AFP, and elevated cell proliferation markers. In addition, this high expression was related to the induction of the Cadherin switch and vimentin expression and was an independent predictor for poor prognosis.

Conclusion: The high expression of FOXC2 in HCC is correlated with tumor malignancy and poor prognosis, suggesting that FOXC2 may be an important prognostic factor for HCC.

Keywords: Epithelial-to-mesenchymal transition; FOXC2; HCC.

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Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the Gunma University school of medicine ethical review board for medical research involving human subjects (Permit Number: 150044). Written informed consent for the collection of specimens and the use of specimens for this study was obtained from all participating patients.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Immunohistochemical analysis of FOXC2, E-cadherin, N-cadherin, and Ki-67 in representative HCC tissues from an identical patient. a High FOXC2 expression in an HCC tissue; b Low E-cadherin expression in an HCC tissue; c High N-cadherin expression in an HCC tissue; d High Ki-67 expression in an HCC tissue. Scale bar, 200 μm
Fig. 2
Fig. 2
Relationship between postoperative survival and FOXC2 expression in 84 patients with HCC. Kaplan–Meier curves of the low expression of FOXC2 and high expression of FOXC2 groups are shown. a A high expression of FOXC2 indicated a poor prognosis for the disease-free survival rate (P = 0.0022). b A high expression of FOXC2 indicated a poor prognosis for the overall survival rate (P = 0.031)
See this image and copyright information in PMC

References

    1. Thun MJ, DeLancey JO, Center MM, Jemal A, Ward EM. The global burden of cancer: priorities for prevention. Carcinogenesis. 2010;31(1):100–110. doi: 10.1093/carcin/bgp263. - DOI - PMC - PubMed
    1. Torrecilla S, Llovet JM. New molecular therapies for hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2015;39(Suppl 1):S80–S85. doi: 10.1016/j.clinre.2015.06.016. - DOI - PubMed
    1. De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 2013;13(2):97–110. doi: 10.1038/nrc3447. - DOI - PubMed
    1. Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S, Baba H, Mori M. Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 2010;101(2):293–299. doi: 10.1111/j.1349-7006.2009.01419.x. - DOI - PMC - PubMed
    1. Kitisin K, Saha T, Blake T, Golestaneh N, Deng M, Kim C, Tang Y, Shetty K, Mishra B, Mishra L. Tgf-Beta signaling in development. Sci STKE. 2007;2007(399):cm1. doi: 10.1126/stke.3992007cm1. - DOI - PubMed

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