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Published in: Journal of Cancer Research and Clinical Oncology 10/2009

01-10-2009 | Original Paper

Expression of hepcidin and other iron-regulatory genes in human hepatocellular carcinoma and its clinical implications

Authors: Hsi-Huang Tseng, Jan-Gowth Chang, Yaw-Huei Hwang, Kun-Tu Yeh, Yao-Li Chen, Hsin-Su Yu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2009

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Abstract

Purpose

We aimed to assess expression of ten iron-regulatory genes in hepatocellular carcinoma (HCC) and its clinical implications.

Methods

We used real-time polymerase chain reaction to measure ten iron-regulatory genes’ mRNA and Perls’ stain to assess iron stores in 50 HCCs and adjacent nontumor specimens. We compared the differences of gene expression and iron stores between tumor and nontumor specimens, and analyzed the relationships of gene expression with hepatic iron stores, patients’ hemoglobin levels and clinicopathologic parameters.

Results

Hepcidin, ceruloplasmin, transferrin, and transferrin receptor 2 were downregulated, while transferrin receptor 1 was upregulated in HCC. Hepcidin was markedly decreased in HCC but still correlated with hepatic iron stores. Iron-regulatory genes varied in their relationships of expression with clinicopathologic parameters.

Conclusions

Altered expression of iron-regulatory genes in HCC may disturb patient’s iron balance. Hepcidin may play a role in defending the body against HCC.
Literature
go back to reference American Joint Committee on Cancer (1997) AJCC cancer staging manual. Lippincott-Raven, Philadelphia American Joint Committee on Cancer (1997) AJCC cancer staging manual. Lippincott-Raven, Philadelphia
go back to reference Andrews NC (2004) Anemia of inflammation: the cytokine–hepcidin link. J Clin Invest 113:1251–1253PubMed Andrews NC (2004) Anemia of inflammation: the cytokine–hepcidin link. J Clin Invest 113:1251–1253PubMed
go back to reference Aoki CA, Rossaro L, Ramsamooj R, Brandhagen D, Burritt MF, Bowlus CL (2005) Liver hepcidin mRNA correlates with iron stores, but not inflammation, in patients with chronic hepatitis C. J Clin Gastroenterol 39:71–74PubMed Aoki CA, Rossaro L, Ramsamooj R, Brandhagen D, Burritt MF, Bowlus CL (2005) Liver hepcidin mRNA correlates with iron stores, but not inflammation, in patients with chronic hepatitis C. J Clin Gastroenterol 39:71–74PubMed
go back to reference Beutler E, Gelbart T, Lee P, Trevino R, Fernandez MA, Fairbanks VF (2000) Molecular characterization of a case of atransferrinemia. Blood 96:4071–4074PubMed Beutler E, Gelbart T, Lee P, Trevino R, Fernandez MA, Fairbanks VF (2000) Molecular characterization of a case of atransferrinemia. Blood 96:4071–4074PubMed
go back to reference Bridle KR, Frazer DM, Wilkins SJ, Dixon JL, Purdie DM, Crawford DHG et al (2003) Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet 361:669–673. doi:10.1016/S0140-6736(03)12602-5 CrossRefPubMed Bridle KR, Frazer DM, Wilkins SJ, Dixon JL, Purdie DM, Crawford DHG et al (2003) Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet 361:669–673. doi:10.​1016/​S0140-6736(03)12602-5 CrossRefPubMed
go back to reference Deugnier YM, Charalambous P, Lequilleuc D, Turlin B, Searle J, Brissot P et al (1993) Preneoplastic significance of hepatic iron-free foci in genetic hemochromatosis: a study of 185 patients. Hepatology 18:1363–1369PubMed Deugnier YM, Charalambous P, Lequilleuc D, Turlin B, Searle J, Brissot P et al (1993) Preneoplastic significance of hepatic iron-free foci in genetic hemochromatosis: a study of 185 patients. Hepatology 18:1363–1369PubMed
go back to reference Hayashi A, Wada Y, Suzuki T, Shimizu A (1993) Studies on familial hypotransferrinemia: unique clinical course and molecular pathology. Am J Hum Genet 53:201–213PubMed Hayashi A, Wada Y, Suzuki T, Shimizu A (1993) Studies on familial hypotransferrinemia: unique clinical course and molecular pathology. Am J Hum Genet 53:201–213PubMed
go back to reference Hirohashi S, Ishak KG, Kojiro M, Wanless IR, Theise ND, Tsukuma H (2000) Hepatocellular carcinoma. In: Hamilton SR, Aaltonen LA et al (eds) World Health Organization classification of tumors, pathology and genetics of tumors of the digestive system. IARC Press, Lyon, pp 165–166 Hirohashi S, Ishak KG, Kojiro M, Wanless IR, Theise ND, Tsukuma H (2000) Hepatocellular carcinoma. In: Hamilton SR, Aaltonen LA et al (eds) World Health Organization classification of tumors, pathology and genetics of tumors of the digestive system. IARC Press, Lyon, pp 165–166
go back to reference Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A et al (2001) Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA 98:8780–8785. doi:10.1073/pnas.151179498 CrossRefPubMed Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A et al (2001) Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA 98:8780–8785. doi:10.​1073/​pnas.​151179498 CrossRefPubMed
go back to reference Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I et al (2002) The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110:1037–1044PubMed Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I et al (2002) The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110:1037–1044PubMed
go back to reference Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P et al (2001) A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 276:7811–7819. doi:10.1074/jbc.M008923200 CrossRefPubMed Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P et al (2001) A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 276:7811–7819. doi:10.​1074/​jbc.​M008923200 CrossRefPubMed
go back to reference Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, Christakis J et al (2003) Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 33:21–22. doi:10.1038/ng1053 CrossRefPubMed Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, Christakis J et al (2003) Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 33:21–22. doi:10.​1038/​ng1053 CrossRefPubMed
go back to reference Searle J, Leggett BA, Crawford DHG, Powell LW (2002) Iron storage diseases. In: MacSween RNM, Burt AD, Portman BC, Ishak KG, Scheuer PJ, Anthony PP (eds) Pathology of the liver, 4th edn. Churchill Livingstone, London, pp 257–272 Searle J, Leggett BA, Crawford DHG, Powell LW (2002) Iron storage diseases. In: MacSween RNM, Burt AD, Portman BC, Ishak KG, Scheuer PJ, Anthony PP (eds) Pathology of the liver, 4th edn. Churchill Livingstone, London, pp 257–272
go back to reference Tseng HH, Hwang YH, Yeh KT, Chang JG, Chen YL, Yu HS (2009) Reduced expression of C/EBPalpha protein in hepatocellular carcinoma is associated with advanced tumor stage and shortened patient survival. J Cancer Res Clin Oncol 135:241–247CrossRefPubMed Tseng HH, Hwang YH, Yeh KT, Chang JG, Chen YL, Yu HS (2009) Reduced expression of C/EBPalpha protein in hepatocellular carcinoma is associated with advanced tumor stage and shortened patient survival. J Cancer Res Clin Oncol 135:241–247CrossRefPubMed
go back to reference Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC (2002) Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 100:3776–3781. doi:10.1182/blood-2002-04-1260 CrossRefPubMed Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC (2002) Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 100:3776–3781. doi:10.​1182/​blood-2002-04-1260 CrossRefPubMed
Metadata
Title
Expression of hepcidin and other iron-regulatory genes in human hepatocellular carcinoma and its clinical implications
Authors
Hsi-Huang Tseng
Jan-Gowth Chang
Yaw-Huei Hwang
Kun-Tu Yeh
Yao-Li Chen
Hsin-Su Yu
Publication date
01-10-2009
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 10/2009
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-009-0585-5

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