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Article

Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma

  • Authors:
    • Hiroshi Wada
    • Hirofumi Yamamoto
    • Chiwan Kim
    • Mamoru Uemura
    • Hirofumi Akita
    • Yoshito Tomimaru
    • Naoki Hama
    • Koichi Kawamoto
    • Shogo Kobayashi
    • Hidetoshi Eguchi
    • Koji Umeshita
    • Yuichiro Doki
    • Masaki Mori
    • Hiroaki Nagano
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan, Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan
  • Pages: 1051-1058
    |
    Published online on: June 24, 2014
       https://doi.org/10.3892/ijo.2014.2519
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Abstract

Hypoxia regulates the expression of genes that promote tumor growth, angiogenesis and invasion. We previously studied hypoxic tumor cells in vitro and from hepatic metastases of colorectal cancer and determined several potential prognostic factors for hepatocellular carcinoma (HCC). In this study, we evaluated the prognostic impact of the expression of ephrin-A1 (EFNA1) and its receptor, EPHA2, in patients with HCC after curative resection. Samples from a total of 139 HCC patients were analyzed by either microarray alone (n=86) or by microarray and quantitative PCR (n=53). There was no correlation between EFNA1 expression and clinicopathological factors. EPHA2 expression was not significantly correlated with any clinicopathological factors, except for microscopic portal invasion. EFNA1 was an independent prognostic factor for HCC (p=0.0277). These findings suggest that EFNA1 expression may be a useful marker for predicting high risk of recurrence in patients who have undergone curative resection for HCC.
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1 

Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet. 362:1907–1917. 2003. View Article : Google Scholar

2 

Semenza GL: Hypoxia and cancer. Cancer Metastasis Rev. 26:223–224. 2007. View Article : Google Scholar

3 

Noda T, Yamamoto H, Takemasa I, et al: PLOD2 induced under hypoxia is a novel prognostic factor for hepatocellular carcinoma after curative resection. Liver Int. 32:110–118. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Maxwell PH and Ratcliffe PJ: Oxygen sensors and angiogenesis. Semin Cell Dev Biol. 13:29–37. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Pugh CW and Ratcliffe PJ: Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med. 9:677–684. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721–732. 2003. View Article : Google Scholar

7 

Zhong H, De Marzo AM, Laughner E, et al: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59:5830–5835. 1999.PubMed/NCBI

8 

Uemura M, Yamamoto H, Takemasa I, et al: Jumonji domain containing 1A is a novel prognostic marker for colorectal cancer: in vivo identification from hypoxic tumor cells. Clin Cancer Res. 16:4636–4646. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Wada H, Nagano H, Yamamoto H, et al: Expression pattern of angiogenic factors and prognosis after hepatic resection in hepatocellular carcinoma: importance of angiopoietin-2 and hypoxia-induced factor-1 alpha. Liver Int. 26:414–423. 2006. View Article : Google Scholar

10 

Yamada D, Kobayashi S, Yamamoto H, et al: Role of the hypoxia-related gene, JMJD1A, in hepatocellular carcinoma: clinical impact on recurrence after hepatic resection. Ann Surg Oncol. 19(Suppl 3): S355–S364. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Hurwitz H, Fehrenbacher L, Novotny W, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 350:2335–2342. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Cheng AL, Kang YK, Chen Z, et al: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10:25–34. 2009. View Article : Google Scholar

13 

Llovet JM, Ricci S, Mazzaferro V, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Vihanto MM, Plock J, Erni D, Frey BM, Frey FJ and Huynh-Do U: Hypoxia up-regulates expression of Eph receptors and ephrins in mouse skin. FASEB J. 19:1689–1691. 2005.PubMed/NCBI

15 

Yamashita T, Ohneda K, Nagano M, et al: Hypoxia-inducible transcription factor-2alpha in endothelial cells regulates tumor neovascularization through activation of ephrin A1. J Biol Chem. 283:18926–18936. 2008. View Article : Google Scholar

16 

Bartley TD, Hunt RW, Welcher AA, et al: B61 is a ligand for the ECK receptor protein-tyrosine kinase. Nature. 368:558–560. 1994. View Article : Google Scholar : PubMed/NCBI

17 

Holzman LB, Marks RM and Dixit VM: A novel immediate-early response gene of endothelium is induced by cytokines and encodes a secreted protein. Mol Cell Biol. 10:5830–5838. 1990.PubMed/NCBI

18 

Brantley DM, Cheng N, Thompson EJ, et al: Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene. 21:7011–7026. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Pandey A, Shao H, Marks RM, Polverini PJ and Dixit VM: Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis. Science. 268:567–569. 1995. View Article : Google Scholar : PubMed/NCBI

20 

Cheng N, Brantley DM, Liu H, et al: Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell growth factor-induced angiogenesis. Mol Cancer Res. 1:2–11. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Deroanne C, Vouret-Craviari V, Wang B and Pouyssegur J: EphrinA1 inactivates integrin-mediated vascular smooth muscle cell spreading via the Rac/PAK pathway. J Cell Sci. 116:1367–1376. 2003. View Article : Google Scholar

22 

Ogawa K, Pasqualini R, Lindberg RA, Kain R, Freeman AL and Pasquale EB: The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization. Oncogene. 19:6043–6052. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Abraham S, Knapp DW, Cheng L, et al: Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder. Clin Cancer Res. 12:353–360. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Brantley-Sieders DM, Fang WB, Hwang Y, Hicks D and Chen J: Ephrin-A1 facilitates mammary tumor metastasis through an angiogenesis-dependent mechanism mediated by EphA receptor and vascular endothelial growth factor in mice. Cancer Res. 66:10315–10324. 2006. View Article : Google Scholar

25 

Liu DP, Wang Y, Koeffler HP and Xie D: Ephrin-A1 is a negative regulator in glioma through downregulation of EphA2 and FAK. Int J Oncol. 30:865–871. 2007.PubMed/NCBI

26 

Nakamura R, Kataoka H, Sato N, et al: EPHA2/EFNA1 expression in human gastric cancer. Cancer Sci. 96:42–47. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Nasreen N, Mohammed KA, Lai Y and Antony VB: Receptor EphA2 activation with ephrinA1 suppresses growth of malignant mesothelioma (MM). Cancer Lett. 258:215–222. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Noblitt LW, Bangari DS, Shukla S, et al: Decreased tumorigenic potential of EphA2-overexpressing breast cancer cells following treatment with adenoviral vectors that express Ephrin-A1. Cancer Gene Ther. 11:757–766. 2004. View Article : Google Scholar

29 

Yamamoto H, Kondo M, Nakamori S, et al: JTE-522, a cyclooxygenase-2 inhibitor, is an effective chemopreventive agent against rat experimental liver fibrosis1. Gastroenterology. 125:556–571. 2003.PubMed/NCBI

30 

Yoshioka S, Takemasa I, Nagano H, et al: Molecular prediction of early recurrence after resection of hepatocellular carcinoma. Eur J Cancer. 45:881–889. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Holm R, de Putte GV, Suo Z, Lie AK and Kristensen GB: Expressions of EphA2 and EphrinA-1 in early squamous cell cervical carcinomas and their relation to prognosis. Int J Med Sci. 5:121–126. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Yamamoto H, Tei M, Uemura M, et al: Ephrin-A1 mRNA is associated with poor prognosis of colorectal cancer. Int J Oncol. 42:549–555. 2013.PubMed/NCBI

33 

Harris AL: Hypoxia - a key regulatory factor in tumour growth. Nat Rev Cancer. 2:38–47. 2002. View Article : Google Scholar : PubMed/NCBI

34 

Iida H, Honda M, Kawai HF, et al: Ephrin-A1 expression contributes to the malignant characteristics of {alpha}-fetoprotein producing hepatocellular carcinoma. Gut. 54:843–851. 2005. View Article : Google Scholar

35 

Cui XD, Lee MJ, Yu GR, et al: EFNA1 ligand and its receptor EphA2: potential biomarkers for hepatocellular carcinoma. Int J Cancer. 126:940–949. 2010.PubMed/NCBI

36 

Miyazaki T, Kato H, Fukuchi M, Nakajima M and Kuwano H: EphA2 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma. Int J Cancer. 103:657–663. 2003. View Article : Google Scholar : PubMed/NCBI

37 

Zelinski DP, Zantek ND, Stewart JC, Irizarry AR and Kinch MS: EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res. 61:2301–2306. 2001.PubMed/NCBI

38 

Zeng G, Hu Z, Kinch MS, et al: High-level expression of EphA2 receptor tyrosine kinase in prostatic intraepithelial neoplasia. Am J Pathol. 163:2271–2276. 2003. View Article : Google Scholar : PubMed/NCBI

39 

Walker-Daniels J, Riese DJ 2nd and Kinch MS: c-Cbl-dependent EphA2 protein degradation is induced by ligand binding. Mol Cancer Res. 1:79–87. 2002.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wada H, Yamamoto H, Kim C, Uemura M, Akita H, Tomimaru Y, Hama N, Kawamoto K, Kobayashi S, Eguchi H, Eguchi H, et al: Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma. Int J Oncol 45: 1051-1058, 2014.
APA
Wada, H., Yamamoto, H., Kim, C., Uemura, M., Akita, H., Tomimaru, Y. ... Nagano, H. (2014). Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma. International Journal of Oncology, 45, 1051-1058. https://doi.org/10.3892/ijo.2014.2519
MLA
Wada, H., Yamamoto, H., Kim, C., Uemura, M., Akita, H., Tomimaru, Y., Hama, N., Kawamoto, K., Kobayashi, S., Eguchi, H., Umeshita, K., Doki, Y., Mori, M., Nagano, H."Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma". International Journal of Oncology 45.3 (2014): 1051-1058.
Chicago
Wada, H., Yamamoto, H., Kim, C., Uemura, M., Akita, H., Tomimaru, Y., Hama, N., Kawamoto, K., Kobayashi, S., Eguchi, H., Umeshita, K., Doki, Y., Mori, M., Nagano, H."Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma". International Journal of Oncology 45, no. 3 (2014): 1051-1058. https://doi.org/10.3892/ijo.2014.2519
Copy and paste a formatted citation
x
Spandidos Publications style
Wada H, Yamamoto H, Kim C, Uemura M, Akita H, Tomimaru Y, Hama N, Kawamoto K, Kobayashi S, Eguchi H, Eguchi H, et al: Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma. Int J Oncol 45: 1051-1058, 2014.
APA
Wada, H., Yamamoto, H., Kim, C., Uemura, M., Akita, H., Tomimaru, Y. ... Nagano, H. (2014). Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma. International Journal of Oncology, 45, 1051-1058. https://doi.org/10.3892/ijo.2014.2519
MLA
Wada, H., Yamamoto, H., Kim, C., Uemura, M., Akita, H., Tomimaru, Y., Hama, N., Kawamoto, K., Kobayashi, S., Eguchi, H., Umeshita, K., Doki, Y., Mori, M., Nagano, H."Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma". International Journal of Oncology 45.3 (2014): 1051-1058.
Chicago
Wada, H., Yamamoto, H., Kim, C., Uemura, M., Akita, H., Tomimaru, Y., Hama, N., Kawamoto, K., Kobayashi, S., Eguchi, H., Umeshita, K., Doki, Y., Mori, M., Nagano, H."Association between ephrin-A1 mRNA expression and poor prognosis after hepatectomy to treat hepatocellular carcinoma". International Journal of Oncology 45, no. 3 (2014): 1051-1058. https://doi.org/10.3892/ijo.2014.2519
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