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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Befeler, A.S., and Di Bisceglie, A.M. 2002. Hepatocellular carcinoma: diagnosis and treatment. Gastroenterology 122: 1609–1619.
Bosch, F.X., Ribes, J., and Borras, J. 1999. Epidemiology of primary liver cancer. Semin. Liver Dis. 19: 271–285.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Llovet, J.M., Schwartz, M., and Mazzaferro, V. 2005. Resection and liver transplantation for hepatocel-lular carcinoma. Semin. Liver Dis. 25: 181–200.
Lo, C.M., and Fan, S.T. 2004. Liver transplantation for hepatocellular carcinoma. Br. J. Surg. 91: 131–133.
Muller, C. 2006. Hepatocellular carcinoma — rising incidence, changing therapeutic strategies. Wien. Med. Wochenshr. 156: 404–409.
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.
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.
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.
Parkin, D.M., Bray, F., Ferlay, J., and Pisani, P. 2001. Estimating the world cancer burden: Globocan 2000. Int. J. Cancer 94: 153–156.
Poon, R.T., and Fan, S.T. 2004. Hepatectomy for hepatocellular carcinoma: patient selection and postoperative outcome. Liver Transpl. 10: S39–S45.
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.
Relaix, F., and Buckingham, M. 1999. From insect eye to vertebrate muscle: redeployment of a regulatory network. Genes Dev. 13: 3171–3178.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer Science + Business Media B.V.
About this chapter
Cite this chapter
Ng, K.TP., Man, K. (2009). Hepatocellular Carcinoma: Overexpression of Homeoprotein Six1 as a Marker for Predicting Survival. In: Hayat, M.A. (eds) Liver Cancer. Methods of Cancer Diagnosis, Therapy and Prognosis, vol 5. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9804-8_24
Download citation
DOI: https://doi.org/10.1007/978-1-4020-9804-8_24
Publisher Name: Springer, Dordrecht
Print ISBN: 978-1-4020-9803-1
Online ISBN: 978-1-4020-9804-8
eBook Packages: MedicineMedicine (R0)