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  • Oncogenomics
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Identification, using cDNA macroarray analysis, of distinct gene expression profiles associated with pathological and virological features of hepatocellular carcinoma

Oncogene volume 21, pages 2926–2937 (2002)Cite this article

Abstract

It is still unclear as to whether the gene expression profile in HCV- or HBV-related HCC exhibits a degree of specificity and whether the development of HCC in a context of cirrhosis influences this gene profile. To address these issues, the expression profiles of 15 cases of HCC were analysed using cDNA macroarray. A global analysis and hierarchical clustering, demonstrated the heterogeneity of HCC patterns, with a majority of down-regulated genes. Statistical analysis clearly showed a distinction between the gene expression profiles of HCV- and HBV-related HCC. HBV-associated HCC exhibited involvement of different cellular pathways, those controlling apoptosis, p53 signalling and G1/S transition. In HCV-related HCC we identified a more heterogenous pattern with an over-expression of the TGF-beta induced gene. In HCC developing on non-cirrhotic tissues, beta-catenin encoding gene and genes implicated in the PKC pathway were specifically up-regulated. In addition, our investigation highlighted a distinct profiles of TGF-beta superfamily encoding genes in well, moderately or poorly differentiated HCC. Overall, our study supports the hypothesis that despite the heterogeneity of the HCC pattern, the large-scale screening of gene expression may provide data significant to our understanding of the mechanism of liver carcinogenesis.

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References

  • Abou-Shady M, Baer HU, Friess H, Berberat P, Zimmermann A, Graber H, Gold LI, Korc M, Buchler MW . 1999 Am. J. Surg. 177: 209–215

  • Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson Jr J, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chang WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM . 2000 Nature 403: 503–511

  • Benvegnu L, Alberti A . 2001 Antiviral Res. 52: 199–207

  • Benvegnu L, Noventa F, Bernardinello E, Pontisso P, Gatta A, Alberti A . 2001 Gut 48: 110–115

  • Bertucci F, Houlgatte R, Benziane A, Granjeaud S, Adelaide J, Tagett R, Loriod B, Jacquemier J, Viens P, Jordan B, Birnbaum D, Nguyen C . 2000 Hum. Mol. Genet. 9: 2981–2991

  • Bradbury LE, Kansas GS, Levy S, Evans RL, Tedder TF . 1992 J. Immunol. 149: 2841–2850

  • Brechot C, Gozuacik D, Murakami Y, Paterlini-Brechot P . 2000 Semin. Cancer Biol. 10: 211–231

  • Buendia MA . 2000 Semin. Cancer Biol. 10: 185–200

  • Clark EA, Golub TR, Lander ES, Hynes RO . 2000 Nature 406: 532–535

  • Delhem N, Sabile A, Gajardo R, Podevin P, Abadie A, Blaton MA, Kremsdorf D, Beretta L, Brechot C . 2001 Oncogene 20: 5836–5845

  • Demetrick DJ, Zhang H, Beach D . 1996 Cytogenet. Cell Genet. 73: 250–254

  • Dotto GP . 2000 Biochim. Biophys. Acta 1471: M43–M56

  • Eisen MB, Spellman PT, Brown PO, Botstein D . 1998 Proc. Natl. Acad. Sci. USA 95: 14863–14868

  • Endo K, Ueda T, Ueyama J, Ohta T, Terada T . 2000 Hum. Pathol. 31: 558–565

  • Fairlie WD, Moore AG, Bauskin AR, Russell PK, Zhang HP, Breit SN . 1999 J. Leukoc. Biol. 65: 2–5

  • Fausto N . 1991 Prog. Growth Factor Res. 3: 219–234

  • Feige JJ, Negoescu A, Keramidas M, Souchelnitskiy S, Chambaz EM . 1996 Horm. Res. 45: 227–232

  • Feo F, Pascale RM, Simile MM, De Miglio MR, Muroni MR, Calvisi D . 2000 Crit. Rev. Oncog. 11: 19–62

  • Francki A, Bradshaw AD, Bassuk JA, Howe CC, Couser WG, Sage EH . 1999 J. Biol. Chem. 274: 32145–32152

  • Garrett SH, Sens MA, Shukla D, Nestor S, Somji S, Todd JH, Sens DA . 1999 Prostate 41: 196–202

  • Gilles C, Bassuk JA, Pulyaeva H, Sage EH, Foidart JM, Thompson EW . 1998 Cancer Res. 58: 5529–5536

  • Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD, Lander ES . 1999 Science 286: 531–537

  • Gozuacik DK, Murakami Y, Saigo K, Chami M, Mugnier C, Lagorce D, Okanoue T, Urashima T, Brechot C, Paterlini-Brechot P . 2001 Oncogene 20: 6233–6240

  • Hayashi J, Aoki H, Arakawa Y, Hino O . 1999 Intervirology 42: 205–210

  • Hegde RS, Voigt S, Rapoport TA, Lingappa VR . 1998 Cell 92: 621–631

  • Hidalgo J, Carrasco J . 1998 Neurotoxicology 19: 661–666

  • Hol FA, van der Put NM, Geurds MP, Heil SG, Trijbels FJ, Hamel BC, Mariman EC, Blom HJ . 1998 Clin. Genet. 53: 119–125

  • Honda M, Kaneko S, Kawai H, Shirota Y, Kobayashi K . 2001 Gastroenterology 120: 955–966

  • Iredale JP, Murphy G, Hembry RM, Friedman SL, Arthur MJ . 1992 J. Clin. Invest. 90: 282–287

  • Ito Y, Matsuura N, Sakon M, Miyoshi E, Noda K, Takeda T, Umeshita K, Nagano H, Nakamori S, Dono K, Tsujimoto M, Nakahara M, Nakao K, Taniguchi N, Monden M . 1999 Hepatology 30: 90–99

  • Juengel JL, Melner MH, Clapper JA, Turzillo AM, Moss GE, Nett TM, Niswender GD . 1998 J. Reprod. Fertil. 113: 299–305

  • Jungmann RA, Huang D, Tian D . 1998 J. Exp. Zool. 282: 188–195

  • Kamai T, Arai K, Tsujii T, Honda M, Yoshida K . 2001 B. J. U. Int. 87: 227–231

  • Kasai Y, Takeda S, Takagi H . 1996 Semin. Surg. Oncol. 12: 155–159

  • Kim HG, Chung YH, Song BC, Kim J, Yang SH, Lee YS, Suh DJ . 2000 Korean J. Intern. Med. 15: 165–170

  • Knight J . 2001 Nature 410: 860–861

  • Kusano N, Shiraishi K, Kubo K, Oga A, Okita K, Sasaki K . 1999 Hepatology 29: 1858–1862

  • Lau WY, Lai PB, Leung MF, Leung BC, Wong N, Chen G, Leung TW, Liew CT . 2000 Oncol. Res. 12: 59–69

  • Laurent-Puig P, Legoix P, Bluteau O, Belghiti J, Franco D, Binot F, Monges G, Thomas G, Bioulac-Sage P, Zucman-Rossi J . 2001 Gastroenterology 120: 1763–1773

  • Le Bail B, Faouzi S, Boussarie L, Balabaud C, Bioulac-Sage P, Rosenbaum J . 1997 J. Pathol. 181: 330–337

  • Liu C, Rangnekar VM, Adamson E, Mercola D . 1998 Cancer Gene Ther. 5: 3–28

  • Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J . 1992 Cell 70: 431–442

  • Miller YE, Minna JD, Gazdar AF . 1989 J. Clin. Invest. 83: 2120–2124

  • Millian NS, Garrow TA . 1998 Arch. Biochem. Biophys. 356: 93–98

  • Mira L, Maia L, Barreira L, Manso CF . 1995 Arch. Biochem. Biophys. 318: 53–58

  • Murakami S . 1999 Intervirology 42: 81–99

  • Nakamura H, Kambe H, Egawa T, Kimura Y, Ito H, Hayashi E, Yamamoto H, Sato J, Kishimoto S . 1989 Clin. Chim. Acta 183: 273–284

  • Nhieu JT, Renard CA, Wei Y, Cherqui D, Zafrani ES, Buendia MA . 1999 Am. J. Pathol. 155: 703–710

  • Okabe H, Satoh S, Kato T, Kitahara O, Yanagawa R, Yamaoka Y, Tsunoda T, Furukawa Y, Nakamura Y . 2001 Cancer Res. 61: 2129–2137

  • Okajima A, Miyazawa K, Naitoh Y, Inoue K, Kitamura N . 1997 Hepatology 25: 97–102

  • Pateron D, Ganne N, Trinchet JC, Aurousseau MH, Mal F, Meicler C, Coderc E, Reboullet P, Beaugrand M . 1994 J. Hepatol. 20: 65–71

  • Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D . 2000 Nature 406: 747–752

  • Podevin P, Sabile A, Gajardo R, Delhem N, Abadie A, Lozach PY, Beretta L, Brechot C . 2001 Hepatology 33: 1503–1511

  • Polette M, Birembaut P . 1998 Int. J. Biochem. Cell Biol. 30: 1195–1202

  • Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B . 1997 Nature 389: 300–305

  • Porte H, Triboulet JP, Kotelevets L, Carrat F, Prevot S, Nordlinger B, DiGioia Y, Wurtz A, Comoglio P, Gespach C, Chastre E . 1998 Clin Cancer Res. 4: 1375–1382

  • Ray RB, Ray R . 2001 FEMS Microbiol. Lett. 202: 149–156

  • Rouault JP, Falette N, Guehenneux F, Guillot C, Rimokh R, Wang Q, Berthet C, Moyret-Lalle C, Savatier P, Pain B, Shaw P, Berger R, Samarut J, Magaud JP, Ozturk M, Samarut C, Puisieux A . 1996 Nat. Genet. 14: 482–486

  • Sato Y, Itoh F, Hareyama M, Satoh M, Hinoda Y, Seto M, Ueda R, Imai K . 1999 J. Gastroenterol. 34: 486–493

  • Schauber C, Chen L, Tongaonkar P, Vega I, Lambertson D, Potts W, Madura K . 1998 Nature 391: 715–718

  • Schulze K, Schultheiss HP . 1995 Eur. Heart J. 16: Suppl O 64–67

  • Shen L, Dean NM, Glazer RI . 1999 Mol. Pharmacol. 55: 396–402

  • Shimotohno K . 2000 Semin. Cancer Biol. 10: 233–240

  • Shirota Y, Kaneko S, Honda M, Kawai HF, Kobayashi K . 2001 Hepatology 33: 832–840

  • Stuver SO . 1998 Semin. Cancer Biol. 8: 299–306

  • Takano T, Hasegawa Y, Miyauchi A, Matsuzuka F, Yoshida H, Kuma K, Amino N . 2001 Cancer Lett. 168: 51–55

  • Takayasu H, Horie H, Hiyama E, Matsunaga T, Hayashi Y, Watanabe Y, Suita S, Kaneko M, Sasaki F, Hashizume K, Ozaki T, Furuuchi K, Tada M, Ohnuma N, Nakagawara A . 2001 Clin. Cancer Res. 7: 901–908

  • Teramoto T, Satonaka K, Kitazawa S, Fujimori T, Hayashi K, Maeda S . 1994 Cancer Res. 54: 231–235

  • Terris B, Pineau P, Bregeaud L, Valla D, Belghiti J, Tiollais P, Degott C, Dejean A . 1999 Oncogene 18: 6583–6588

  • Thorgeirsson SS, Teramoto T, Factor VM . 1998 Semin. Liver Dis. 18: 115–122

  • Tornillo L, Carafa V, Richter J, Sauter G, Moch H, Minola E, Gambacorta M, Bianchi L, Vecchione R, Terracciano LM . 2000 J. Pathol. 192: 307–312

  • Veneziani BM, Villone G, Romano R, Di Carlo A, Garbi C, Tramontano D . 1990 J. Cell Biol. 111: 2703–2711

  • Vousden KH . 2000 Cell 103: 691–694

  • Weissman AM . 2001 Nat. Rev. Mol. Cell Biol. 2: 169–178

  • Welsh JB, Zarrinkar PP, Sapinoso LM, Kern SG, Behling CA, Monk BJ, Lockhart DJ, Burger RA, Hampton GM . 2001 Proc. Natl. Acad. Sci. USA 98: 1176–1181

  • Wong CM, Fan ST, Ng IO . 2001 Cancer 92: 136–145

  • Xu L, Hui L, Wang S, Gong J, Jin Y, Wang Y, Ji Y, Wu X, Han Z, Hu G . 2001 Cancer Res. 61: 3176–3181

  • Yamashita T, Kaneko S, Hashimoto S, Sato T, Nagai S, Toyoda N, Suzuki T, Kobayashi K, Matsushima K . 2001 Biochem. Biophys. Res. Commun. 282: 647–654

  • Yuspa SH, Dlugosz AA, Cheng CK, Denning MF, Tennenbaum T, Glick AB, Weinberg WC . 1994 J. Invest. Dermatol. 103: 90S–95S

  • Zhan Q, Bae I, Kastan MB, Fornace Jr AJ . 1994 Cancer Res. 54: 2755–2760

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Acknowledgements

We would like to thank the following for their invaluable help in collecting human liver samples: Prof Dominique Franco, Dr Cyrille Feray and all the Pathological Anatomy Department at the Antoine Beclere and Paul Brousse Hospitals. We would like to thank Yves Chretien for advice on statistical analysis, Dominique Daudry and Fanny Baran-Marszak for providing primer sequences and PCR conditions. This work was supported by grants from Institut National de la Recherche Médicale (INSERM), from the Ligue contre le Cancer (LNC), from Association pour la Recherche contre le Cancer (ARC) and from the European Community. Oona Delpuech was supported by a fellowship from Agence Nationale de la Recherche sur le Sida (ANRS).

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  1. INSERM U370, CHU Necker/Institut Pasteur, Paris, 75015, France

    Oona Delpuech, Jean-Baptiste Trabut, Christian Brechot & Dina Kremsdorf

  2. Service d'Anatomo-Pathologie, Hôpital Européen Georges Pompidou, Paris, 75015, France

    Françoise Carnot

  3. Service d'Hématologie Biologique et EA ATHSCO, Hôpital Avicenne, Bobigny, 93009, France

    Jean Feuillard

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  1. Oona Delpuech
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Correspondence to Dina Kremsdorf.

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Delpuech, O., Trabut, JB., Carnot, F. et al. Identification, using cDNA macroarray analysis, of distinct gene expression profiles associated with pathological and virological features of hepatocellular carcinoma. Oncogene 21, 2926–2937 (2002). https://doi.org/10.1038/sj.onc.1205392

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