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Proteomics of Hepatocellular Carcinoma: Present Status and Future Prospects

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Proteomics: Biomedical and Pharmaceutical Applications

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Conclusions

Proteome analysis of HCC is an emerging area of research in the discovery of novel proteins as early biomarkers for diagnosis and potential therapeutic targets for the treatment of HCC. Although numerous publications have appeared on the gene expression analysis of HCC by cDNA microarrays, there is still a need to analyze the differentially expressed proteins in the cellular proteome as many protein modifications are not reflected by changes at the RNA level. New and improved proteomic technologies such as DIGE, and ICAT labelling in combination with mass spectrometric analysis will drive and accelerate the next phase of expression profiling of HCC. There will also be a concerted effort in performing proteome analysis at the subcellular level (subproteomics) in order to detect and identify low abundance proteins which may be missed at the global expression profile of the whole cell. In addition the localization sites of these identified proteins will provide clues to their functions. Finally, it is hoped that integration of proteome-based approaches with data from genomic profiling will lead to a better understanding of hepatocarcinogenesis which will then contribute to the direct translation of the research findings into clinical practice (Selinger and Kellner, 2002).

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References

  • Beasley, R.P., Hwang, L.Y., Lin, C.C., and Chien, C.S., 1981, Hepatocellular carcinoma and hepatitis B virus: a prospective study of 22707 men in Taiwan. Lancet, 2: 1129–1133.

    CAS  PubMed  Google Scholar 

  • Chen, X., Cheung, S.T., So, S., Fan, S.T., Barry, C., Higgins, J., Lai, K.-M., Ji, J., Dudoit, S., Ng, I.O.L., van de Rijn, M., Botstein, D., and Brown, P.O., 2002, Gene expression patterns in human liver cancers. Mol. Biol. Cell, 13: 1929–1939.

    CAS  PubMed  Google Scholar 

  • Cho, S.Y., Park, K.-S., Shim, J.E., Kwon, M.-S., Joo, K.H., Lee, W.S., Chang, J., Kim, H., Chung, H.C., Kim, H.O., Paik, Y.-K., 2002, An integrated proteome database for two-dimensional electrophoresis data analysis and laboratory information management system. Proteomics, 2: 1104–1113.

    Article  CAS  PubMed  Google Scholar 

  • Choong, M.L., Tan, L.K., Lo, S.L., Ren, E.C., Ou, K., Ong, S.-E., Liang, R.C.M.Y., Seow, T.K., and Chung, M.C.M., 2001, An integrated approach in the discovery and characterization of a novel nuclear protein over-expressed in liver and pancreatic tumours. FEBS Letts., 496: 109–116.

    Article  CAS  Google Scholar 

  • Delpuech, O., Trabut, J.-P., Carnot, F., Feuillard, J., Brechot, C., and Kremsdorf, D., 2002, Identification, using cDNA macroarray analysis, of distinct gene expression profiles associated with pathological and virological features of hepatocellular carcinoma. Oncogene, 21: 2926–2937.

    Article  CAS  PubMed  Google Scholar 

  • Deuffic, S., Buffat, L., Poynard, T., and Valleron, A.J., 1999, Modeling the hepatitis C virus epidemic in France. Hepatology, 29: 1596–1601.

    Article  CAS  PubMed  Google Scholar 

  • Dreger, M., 2003, Proteome analysis at the level of subcellular structures. Eur. J. Biochem., 270: 589–599.

    CAS  PubMed  Google Scholar 

  • Du, M.Q., Hutchinson, W.L., Johnson, P.J., and Williams, R., 1991, Differential α-fetoprotein lectin binding in hepatocellular carcinoma. Cancer, 61: 476–480.

    Google Scholar 

  • El-Serag, H.B. and Mason, A.C., 1999, Rising incidence of hepatocellular carcinoma in the United States. N. England J. Med., 340: 745–750.

    CAS  Google Scholar 

  • Feitelson, M.A., Sun, B., Tufan, N.L.G., Liu, J., and Lian, Z., 2002, Genetic mechanisms of hepatocarcinogenesis. Oncogene, 21: 2593–2604.

    Article  CAS  PubMed  Google Scholar 

  • Fukuda, S., Wu, D.W., Stark, K., and Pelus, L.M., 2002, Cloning and characterization of a proliferation-associated cytokine-inducible protein, CIP29. Biochem. Biophys. Res. Commun., 292: 593–600.

    Article  CAS  PubMed  Google Scholar 

  • Goldenberg, D., Ayesh, S., Schneider, T., Pappo, O., Jurim, O., Eid, A., Fellig, Y., Dadon, T., Ariel, I., de Groot, N., Hochberg, A., and Galun, E., 2002, Analysis of differentially expressed genes in hepatocellular carcinoma using cDNA arrays. Molec. Carcinog., 33: 113–124.

    CAS  Google Scholar 

  • Gray, S.G., 2001, Proteomic payoff. Trends in Genetics, 17: 382–382.

    Google Scholar 

  • Gygi, S.P., Rochon, Y., Franza, B.R., and Aebersold, R., 1999a, Correlation between protein and mRNA abundance in yeast. Mol. Cell. Biol., 19: 1720–1730.

    CAS  PubMed  Google Scholar 

  • Gygi, S.P., Rist, B., Gerber, S.A., Turecek, F., Gelb, M.H., and Aebersold, R., 1999b, Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nature Biotechnol., 17: 994–999.

    Article  CAS  Google Scholar 

  • Ho, S., Cheng, P., Chan, A., Leung, N., Yeo, W., Leung, T., Lau, W.Y., Li, A.K.C. and Johnson, P.J., 1996, Isoelectric focusing of alpha-fetoprotein in patients with hepatocellular carcinoma — frequency of specific banding patterns at non-diagnostic serum levels. Brit. J. Cancer, 73: 985–988.

    CAS  PubMed  Google Scholar 

  • Ideker, T., Thorsson, V., Ranish, J.A., Christmas, R., Buhler, J., Eng, J.K., Bumgarner, R., Goodlett, D.R., Aebersold, R., and Hood, L., 2001, Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science, 292: 929–934.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, P.J., Leung, N., Cheng, P., Welby, C., Leung, T., Lau, W.Y., Yu, S., and Ho, S., 1997, ‘Hepatoma-specific’ alpha-fetoprotein may perrmit preclinical diagnosis of malignant change in patients with chronic liver disease. Brit. J. Cancer, 75: 236–242.

    CAS  PubMed  Google Scholar 

  • Kao, J.-H. and Chen, D.-S., 2002, Recent updates in hepatitis vaccination and the prevention of hepatocellular carcinoma. Int. J. Cancer, 97: 269–271.

    Article  CAS  PubMed  Google Scholar 

  • Kim, J., Kim, SA.H., Lee, S.U., Ha, G.H., Kang, D.G., Ha, N.-H., Ahn, J.S., Cho, H.Y., Kang, S.-J., Lee, W.-J., Hong, H.C., Ha, W.S., Bae, J.M., Lee, C.-W., and Kim, J.W., 2002, Proteome analysis of human liver tissue by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization mass spectrometry for identification of diseaserelated proteins. Electrophoresis, 23: 4142–4156.

    CAS  PubMed  Google Scholar 

  • Kim, M.-Y., Park, E., Park, J.-H., Park, D.-H., Moon, W.-S., Cho, B.-H., Shin, H.-S., and Kim, D.-G., 2001, Expression profile of nine novel genes differentially expressed in hepattis B virus-associated hepatocellular carcinomas. Oncogene, 20: 4568–4575.

    CAS  PubMed  Google Scholar 

  • Lau, W.-Y., Lai, P.B.S., Leung, M.-F., Leung, B.C.S., Wong, N., Chen, G., Leung, T.W.T., and Liew, C.-T., 2000, Differential gene expression of hepatocellular carcinoma using cDNA microarray analysis. Oncology Res., 12: 59–69.

    CAS  Google Scholar 

  • Le Naour, F., Brichory, F.B., Misek, D.E., Brechoy, C., Hanash, S.M., and Beretta, L., 2002, A distinct repertoire of autoantibodies in hepatocellular carcinoma identified by proteomic analysis. Mol.Cell.Proteomics, 1.3: 197–203.

    Google Scholar 

  • Li, D., Mallory, T., and Satomura, S., 2001, ALF-L3: a new generation of tumour marker for hepatocellular carcinoma. Clin. Chim. Acta, 313: 15–19.

    CAS  PubMed  Google Scholar 

  • Liang, R.C.M.Y., Neo, J.C.H., Lo, S.L., Tan, G.S., Seow, T.K., and Chung, M.C.M., 2002, Proteome database of hepatocellular carcinoma. J. Chrom. B, 771: 303–328.

    CAS  Google Scholar 

  • Lim, S,O., Park, S.-J., Kim, W., Park, S.G., Kim, H.-J., Kim, Y.-I., Sohn, T.-S., Noh, J.-H., and Jung, G., 2002, Proteome analysis of hepatocellular carcinoma. Biochem. Biophys. Res. Comm., 291: 1031–1037.

    Article  CAS  PubMed  Google Scholar 

  • Llovet, J.M. and Beaugrand, M., 2003, Hepatocellular carcinoma: present status and future prospects. J. Hepatology, 38: S136–S149.

    Article  Google Scholar 

  • McGlynn, K.A., Tsao, L., Hsing, A.W., Devesa, S.S., and Fraumeni, Jr., J.F., 2001, International trends and patterns of primary liver cancer. Int. J. Cancer, 94: 290–296.

    Article  CAS  PubMed  Google Scholar 

  • Naraki, T., Kohno, N., Saito, H., Fujimoto, Y., Ohhira, M., Morita, T. and Kohgo, Y., 2002, γ-Carboxyglutamic acid content of hepatocellular carcinoma-associated des-γ-carboxy prothrombin. Biochim. Biophys. Acta, 1586: 287–298.

    CAS  PubMed  Google Scholar 

  • Okabe, H., Satoh, S., Kato, T., Kitahara, O., Yanagawa, R., Yamaoka, Y., Tsunoda, T., Furukawa, Y., and Nakamura, Y., 2001, Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumour progression. Cancer Res., 61: 2129–2137.

    CAS  PubMed  Google Scholar 

  • Old, L.J., and Chen, Y.T., 1998, New paths in human cancer serology. J. Exp. Med., 187: 1163–1167.

    Article  CAS  PubMed  Google Scholar 

  • Ou, K., Seow, T.K., Liang, R.C.M.Y., Ong, S.-E., and Chung, M.C.M., 2001, Proteome analysis of a human hepatocellular carcinoma cell line, HCC-M: An update. Electrophoresis, 22: 2804–2811.

    CAS  PubMed  Google Scholar 

  • Park, K.-S., Cho, S.-Y., Kim, H., and Paik, Y.-K., 2002, Proteomic alterations of the variants of human aldehyde dehydrogenase isozymes correlate with hepatocellular carcinoma. Int. J. Cancer, 97: 261–265.

    Article  CAS  PubMed  Google Scholar 

  • Parkin, D.M., Bray, F., Ferlay, J., and Pisani, P., 2001, Estimating the world cancer burden: Globocan 2000. Int J. Cancer, 94: 153–156.

    Article  CAS  PubMed  Google Scholar 

  • Poon, T.C.W., and Johnson, P.J., 2001, Proteome analysis and its impact on the discovery of serological tumour markers. Clin. Chim. Acta, 313: 231–239.

    CAS  PubMed  Google Scholar 

  • Poon, T.C.W., Mok, T.S.K., Chan, A.T.C., Chan, C.M.L., Leong, V., Tsui, S.H.T., Leung, T.W.T., Wong, H.T.M., Ho, S.K.W. and Johnson, P.J., 2002, Quantitation and utility of monosialylated α-fetoprotein in the diagnosis of hepatocellular carcinoma with nondiagnostic serum total α-fetoprotein. Clin. Chemistry, 48: 1021–1027.

    CAS  Google Scholar 

  • Sahin, U., Tureci, O., Schmitt, H., Cochlovius, B., Johannes, T., Schmits, R., Stenner, F., Luo, G., Schobert, I., and Pfreundschuh., 1995, Human neoplasms elicit multiple specific immune responses in the autologous host. Proc. Natl. Acad. Sci., 92: 1180–1183.

    Google Scholar 

  • Saitoh, S., Ikeda, K., Koida, I., Tsubota, A., Arase, Y., Chayama, K. and Kumada, H., 1994, Serum des-gamma-carboxy prothrombin concentration determination by avidin-biotin complex in small hepatocellular carcinomas. Cancer, 74: 2918–2923.

    CAS  PubMed  Google Scholar 

  • Schafer, D.F., and Sorrell, M.F., 1999, Hepatocellular carcinoma. Lancet, 353: 1253–1257.

    Article  CAS  PubMed  Google Scholar 

  • Selinger, B., and Kellner, R., 2002, Design of proteome-based studies in combination with serology for the identification of biomarkers and novel targets. Proteomics, 2: 1641–1651.

    Google Scholar 

  • Seow, T.K., Ong, S.-E., Liang, R.C.M.Y., Ren, E.-C., Chan, L., Ou, K., and Chung, M.C.M., 2000, Two-dimensional electrophoresis map of the human hepatocellular carcinoma cell libe, HCC-M, and identification of the separated proteins by mass spectrometry. Electrophoresis, 21: 1787–1813.

    Article  CAS  PubMed  Google Scholar 

  • Seow, T.K., Liang, R.C.M.Y., Leow, C.K., and Chung, M.C.M., Hepatocellular carcinoma: from bedside to proteomics. Proteomics, 1: 1249–1263.

    Google Scholar 

  • Shirota, Y., Kaneko, S., Honda, M., Kawai, H.F., and Kobayashi, K., 2001, Identification of differentially expressed genes in hepatocellular carcinoma with cDNA microarrays. Hepatology, 33: 832–840.

    Article  CAS  PubMed  Google Scholar 

  • Simpson, R.J., and Dorow, D.S., 2001, Cancer proteomics: from signalling networks to tumour markers. Trends in Biotechnol, 19: S40–S48.

    CAS  Google Scholar 

  • Steel, L.F., Mattu, T.S., Mehta, A., Hebestreit, H., Dwek, R., Evans, A.A., London, W.L., and Block, T., 2001, A proteomic approach for the discovery of early detection markers of hepatocellular carcinoma. Dis. Markers, 17: 179–189.

    CAS  PubMed  Google Scholar 

  • Stenner-Liewen, F., Luo, G., Sahin, U., Tureci, O., Koslovski, I., Kautz, I., Liewen, H., and Pfreundschuh, M., 2000, Definition of tumour-associated antigens in hepatocellular carcinoma. Cancer Epidemiol. Biomarkers Prev., 9: 285–290.

    CAS  PubMed  Google Scholar 

  • Tackels-Horne, D., Goodman, M.D., Williams, A.J., Wilson, D.J., Eskandari, T., Vogt, L.M., Boland, J.F., Scherf, U., and Vockley, J.G., 2001, Identification of differentially expressed genes in hepatocellular carcinoma and metastatic liver tumors by oligonucleotide expression profiling. Cancer, 92: 395–405.

    Article  CAS  PubMed  Google Scholar 

  • Thorgeirsson S.S. and Grisham, J.W., 2002, Molecular pathogenesis of human hepatocellular carcinoma. Nature Genetics, 31: 339–346.

    Article  CAS  PubMed  Google Scholar 

  • Tonge, R., Shaw, J., Middleton, B., Rowlinson, R., Rayner, S., Young, J., Pognan, F., Hawkins, E., Currie, I., and Davison, M. 2001, Validation and development of fluorescent two-dimensional differential gel electrophoresis proteomics technology. Proteomics, 1: 377–396.

    Article  CAS  PubMed  Google Scholar 

  • Unlu, M., Morgan, M.E., and Minden, J.S., 1997, Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis, 18: 2071–2077.

    CAS  PubMed  Google Scholar 

  • Wang, Y., Han, K.-J., Pang, X.-W., Vaughan, H.A., Qu, W., Dong, X.-Y., Peng, J.-R., Zhao, H.-T., Rui, J.-A., Leng, X.-S., Cebon, J., Burgess, A.W., and Chen, W.-F., 2002, Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies. J. Immunol., 169: 1102–1109.

    CAS  PubMed  Google Scholar 

  • Watanabe, T., Morizane, T., Tsuchimoto, K., Inagaki, Y., Munakata, Y., Nakamura, T., Kumagai, N., and Tsuchiya, M., 1983, Establishment of a cell line (HCC-M) from a human hepatocellular carcinoma. Int.J. Cancer, 32: 141–146.

    CAS  PubMed  Google Scholar 

  • Wirth, P.J., Hoang, T.N., and Benjamin, T., 1995, Micropreparative immobilized pH gradient two-dimensional electrophoresis in combination with protein microsequencing for the analysis of human liver proteins. Electrophoresis, 16: 1946–1960.

    Article  CAS  PubMed  Google Scholar 

  • Xu, X.-R., Huang, J., Xu, Z.-G., Qian, B.-Z., Zhu, Z.-D., Yan, Q., Cai, T., Zhang, X., Xiao, H.-S., Qu, J., Liu, F., Huang, Q.-H., Cheng, Z.-H., Li, N.-G., Du, J.-J., Hu, W., Shen, K.-T., Lu, G., Zhong, M., Xu, S.-H., Gu, W.-Y., Huang, W., Zhao, X.T., Hspu, G.-X., Gu, J.-R., Chen, Z., and Han, Z.-G., 2001, Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver. Proc. Natl. Acad. Sci., 98: 15089–15094.

    CAS  PubMed  Google Scholar 

  • Yano, N., Habib, N.A., Fadden, K.J., Yamashita, H., Mitry, R., Jauregui, H., Kane, A., Endoh, M., and Rifai, A., 2001, Profiling of the human adult liver transcriptome: analysis by cDNA array hybridization. J. Hepatology, 35: 178–186.

    Article  CAS  Google Scholar 

  • Yu, L.-R., Zeng, R., Shao, X.-X., Wang, N., Xu, Y.-H., Xia, Q.-C., 2000, Identification of differentially expressed proteins between human hepatoma and normal liver cell lines by two-dimensional electrophoresis and liquid chromatography-ion trap mass spectrometry. Electrophoresis, 21: 3058–68.

    CAS  PubMed  Google Scholar 

  • Yu, L.-R., Shao, X.-X., Jiang, W.-L., Xu, D., Chang, Y.-C., Xu, Y.-H., and Xia, Q.-C., 2001, Proteome alterations in human hepatoma cells transfected with antisense epidermal growth factor receptor sequence. Electrophoresis, 22: 3001–3008.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore, 119260, Republic of Singapore

    Maxey C. M. Chung

  2. Department of Biological Science, Faculty of Science, National University of Singapore, Singapore, 119260, Republic of Singapore

    Rosa C. M. Y. Liang, Teck Keong Seow, Jason C. H. Neo, Siaw Ling Lo & Gek San Tan

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  1. University of Sciences and Technologies, Lille, France

    Hubert Hondermarck

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Chung, M.C.M., Liang, R.C.M.Y., Seow, T.K., Neo, J.C.H., Lo, S.L., Tan, G.S. (2004). Proteomics of Hepatocellular Carcinoma: Present Status and Future Prospects. In: Hondermarck, H. (eds) Proteomics: Biomedical and Pharmaceutical Applications. Springer, Dordrecht. https://doi.org/10.1007/1-4020-2323-5_7

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