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Liver Cancer pp 313-323 | Cite as

Hepatocellular Carcinoma: Overexpression of Homeoprotein Six1 as a Marker for Predicting Survival

  • Kevin Tak-Pan Ng
  • Kwan Man
Chapter
  • 1.6k Downloads
Part of the Methods of Cancer Diagnosis, Therapy and Prognosis book series (HAYAT, volume 5)

Hepatocellular carcinoma (HCC) which occurs in 80% of all primary liver is the fifth most common cancer and the third most common cause of death from cancer in the world (Parkin et al., 2001; Befeler and Di Bisceglie, 2002). The incident rate of HCC, which is highest in Asia and Africa, is increasing in Western countries. In the United States, 19,160 new cancers of the liver and intrahepatic bile duct were estimated in 2007, with an estimated 16,780 deaths (Jemal et al., 2007). Chronic hepatitis B infection is the most common cause of HCC in China and Southeast Asia (Muller, 2006), while hepatitis C infection is of high importance in Europe, Japan and North America (Bosch et al., 1999). Other common risk factors for hepatocar-cinogenesis include alcohol, aflatoxin ²1, cirrhosis, ±-1-antitrypsin deficiency and hereditary hemochromatosis. Currently, there is no standard treatment for advanced HCC. Surgical treatments, including hepa-tectomy and liver transplantation, are major curative options for HCC. However, long-term survival rate remains unsatisfactory due to tumor recurrence and metastasis (Poon and Fan, 2004; Lo and Fan, 2004; Llovet et al., 2005). For better stratification and management of HCC patients, identification of potential markers for accurate prognosis of HCC patients in terms of malignancy and survival rate is indispensable.

Keywords

Normal Liver Tissue Hereditary Hemochromatosis Nontumor Tissue pTNM Stage Six1 Gene 
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.

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References

  1. Befeler, A.S., and Di Bisceglie, A.M. 2002. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology 122: 1609–1619.PubMedCrossRefGoogle Scholar
  2. Bosch, F.X., Ribes, J., and Borras, J. 1999. Epidemiology of primary liver cancer. Semin. Liver Dis. 19: 271–285.PubMedCrossRefGoogle Scholar
  3. Chao, Y., Shih, Y.L., Chiu, J.H., Chau, G.Y., Lui, W.Y., Yang, W.K., Lee, S.D., and Huang, T.S. 1998. Overexpression of cyclin A but not Skp 2 correlates with the tumor relapse of human hepa-tocellular carcinoma. Cancer Res. 58: 985–990.PubMedGoogle Scholar
  4. Coletta, R.D., Christensen, K., Reichenberger, K.J., Lamb, J., Micomonaco, D., Huang, L., Wolf, D.M., Muller-Tidow, C., Golub, T.R., Kawakami, K., and Ford, H.L. 2004. The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1. Proc. Natl. Acad. Sci. USA 101: 6478–6483.PubMedCrossRefGoogle Scholar
  5. Fields, A.C., Cotsonis, G., Sexton, D., Santoianni, R., and Cohen, C. 2004. Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome. Mod. Pathol. 17: 1378–1385.PubMedCrossRefGoogle Scholar
  6. Ford, H.L., Kabingu, E.N., Bump, E.A., Mutter, G.L., and Pardee, A.B. 1998. Abrogation of the G2 cell cycle checkpoint associated with over-expression of HSIX1: a possible mechanism of breast carcinogenesis. Proc. Natl. Acad. Sci. USA 95: 12608–12613.PubMedCrossRefGoogle Scholar
  7. Ford, H.L., Landesman-Bollag, E., Dacwag, C.S., Stukenberg, P.T., Pardee, A.B., and Seldin, D.C. 2000. Cell cycle-regulated phosphorylation of the human SIX1 homeodomain protein. J. Biol. Chem. 275: 22245–22254.PubMedCrossRefGoogle Scholar
  8. Gavin, L.G., Romieu-Mourez, R., Panta, G.R., Sun, J., Factor, V.M., Thorgeirsson, S.S., Sonenshein, G.E., and Arsura, M. 2003. Inhibition of CK2 activity by TGF-beta1 promotes IkappaB-alpha protein stabilization and apoptosis of immortalized hepatocytes. Hepatology 38: 1540–1551.Google Scholar
  9. Ikeguchi, M., Ueda, T., Sakatani, T., Hirooka, Y., and Kaibara, N. 2002. Expression of survivin messenger RNA correlates with poor prognosis in patients with hepatocellular carcinoma. Diagn. Mol. Pathol. 11: 33–40.PubMedCrossRefGoogle Scholar
  10. Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., and Thun, M.J. 2007. Cancer statistics 2007. CA. Cancer J. Clin. 57: 43–66.PubMedCrossRefGoogle Scholar
  11. Laclef, C., Hamard, G., Demignon, J., Souil, E., Houbron, C., and Maire, P. 2003. Altered myo-genesis in Six1-deficient mice. Development 130: 2239–2252.PubMedCrossRefGoogle Scholar
  12. Lee, T.K., Man, K., Poon, R.T., Lo, C.M., Yuen, A.P., Ng, I.O., Ng, K.T., Leonard, W., and Fan, S.T. 2006. Signal transducers and activators of transcription 5b activation enhances hepatocellu-lar carcinoma aggressiveness through induction of epithelial-mesenchymal transition. Cancer Res. 66: 9948–9956.PubMedCrossRefGoogle Scholar
  13. Li, C.M., Guo, M., Borczuk, A., Powell, C.A., Wei, M., Thaker, H.M., Friedman, R., Klein, U., Tycko, B. 2002. Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition. Am. J. Pathol. 160: 2181–2190.PubMedGoogle Scholar
  14. Li, Y., Tang, Z.Y., Ye, S.L., Liu, Y.K., Chen, J., Xue, Q., Chen, J., Gao, D.M., and Bao, W.H. 2001. Establishment of cell clones with different potential from the hepatocellular carcinoma cell line MHCC97. World J. Gastroenterol. 7: 630–636.PubMedGoogle Scholar
  15. Llovet, J.M., Schwartz, M., and Mazzaferro, V. 2005. Resection and liver transplantation for hepatocel-lular carcinoma. Semin. Liver Dis. 25: 181–200.PubMedCrossRefGoogle Scholar
  16. Lo, C.M., and Fan, S.T. 2004. Liver transplantation for hepatocellular carcinoma. Br. J. Surg. 91: 131–133.PubMedCrossRefGoogle Scholar
  17. Muller, C. 2006. Hepatocellular carcinoma — rising incidence, changing therapeutic strategies. Wien. Med. Wochenshr. 156: 404–409.CrossRefGoogle Scholar
  18. Ohashi, R., Gao, C., Miyazaki, M., Hamazaki, K., Tsuji, T., Inoue, Y., Uenura, T., Hirai, R., Shimizu, N., and Namba, M. 2001. Enhanced expression of cyclin E and cyclin A in human hepatocellular carcinomas. Anticancer Res. 21: 657–662.PubMedGoogle Scholar
  19. Oliver, G., Wehr, R., Jenkins, N.A., Copeland, N.G., Cheyette, B.N., Hartenstein, V., Zipursky, S.L., and Gruss, P. 1995. Homeobox genes and connective tissue patterning. Development 121: 693–705.PubMedGoogle Scholar
  20. Ozaki, H., Nakamura, K., Funahashi, J., Ikeda, K., Yamada, G., Tokano, H., Okamura, H.O., Kitamura, K., Muto, S., Kotaki, H., Sudo, K., Horai, R., Iwakura, Y., and Kawakami, K. 2004. Six1 controls patterning of the mouse otic vesicle. Development 131: 551–562.PubMedCrossRefGoogle Scholar
  21. Parkin, D.M., Bray, F., Ferlay, J., and Pisani, P. 2001. Estimating the world cancer burden: Globocan 2000. Int. J. Cancer 94: 153–156.PubMedCrossRefGoogle Scholar
  22. Poon, R.T., and Fan, S.T. 2004. Hepatectomy for hepatocellular carcinoma: patient selection and postoperative outcome. Liver Transpl. 10: S39–S45.PubMedCrossRefGoogle Scholar
  23. Reichenberger, K.J., Coletta, R.D., Schulte, A.P., Varella-Garcia, M., and Ford, H.L. 2005. Gene amplification is a mechanism of Six 1over-expression in breast cancer. Cancer Res. 65: 2668–2675.PubMedCrossRefGoogle Scholar
  24. Relaix, F., and Buckingham, M. 1999. From insect eye to vertebrate muscle: redeployment of a regulatory network. Genes Dev. 13: 3171–3178.PubMedCrossRefGoogle Scholar
  25. Ueki, T., Fujimoto, J., Suzuki, T., Yamamoto, H., and Okamoto, E. 1997. Expression of hepatocyte growth factor and its receptor c-met proto-onco-gene in hepatocellular carcinoma. Hepatology 25: 619–623.PubMedCrossRefGoogle Scholar
  26. Xu, P.X., Zheng, W., Huang, L., Maire, P., Laclef, C., and Silvius, D. 2003. Six1 is required for the early organogenesis of mammalian kidney. Development 130: 3085–3094.PubMedCrossRefGoogle Scholar
  27. Yu, Y., Davicioni, E., Triche, T.J., and Merlino, G. 2006. The homeoprotein six1 transcriptionally activates multiple protumorigenic genes but requires ezrin to promote metastasis. Cancer Res. 66: 1982–1989.PubMedCrossRefGoogle Scholar
  28. Yu, Y.L., Khan, J., Khanna, C., Helman, L., Meltzer, P.S., and Merlino, G. 2004. Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeopro-tein Six-1 as key regulators. Nat. Med. 10: 175–181.PubMedCrossRefGoogle Scholar
  29. Zheng, W., Huang, L., Wei, Z.B., Silvius, D., Tang, B., and Xu, P.X. 2003. The role of Six1 in mammalian auditory system development. Development 130: 3989–4000.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media B.V. 2009

Authors and Affiliations

  • Kevin Tak-Pan Ng
    • 1
  • Kwan Man
    • 1
  1. 1.Center for the Study of Liver Disease and Department of SurgeryThe University of Hong Kong, Queen Mary HospitalPokfulamRepublic of China

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