Couvert P, Carrié A, Pariès J, Vaysse J, Miroglio A, Kerjean A, Nahon P, Chelly J, Trinchet JC, Beaugrand M, Ganne-Carrié N. Liver insulin-like growth factor 2 methylation in hepatitis C virus cirrhosis and further occurrence of hepatocellular carcinoma. World J Gastroenterol 2008; 14(35): 5419-5427 [PMID: 18803353 DOI: 10.3748/wjg.14.5419]
Corresponding Author of This Article
Dr. Nathalie Ganne-Carrié, Department of Hepato-Gastroenterology, Jean Verdier Hospital, AP-HP, Bondy 93140, France. nathalie.ganne@jvr.aphp.fr
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Rapid Communication
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World J Gastroenterol. Sep 21, 2008; 14(35): 5419-5427 Published online Sep 21, 2008. doi: 10.3748/wjg.14.5419
Liver insulin-like growth factor 2 methylation in hepatitis C virus cirrhosis and further occurrence of hepatocellular carcinoma
Philippe Couvert, Alain Carrié, Jacques Pariès, Jenny Vaysse, Audrey Miroglio, Antoine Kerjean, Pierre Nahon, Jamel Chelly, Jean-Claude Trinchet, Michel Beaugrand, Nathalie Ganne-Carrié
Philippe Couvert, Alain Carrié, INSERM U551, Dyslipopro-teinemia and Atherosclerosis Research Unit, Paris F-75013, France; Université Paris6, UMR S551, Paris F-75013, France; AP-HP, Groupe hospitalier Pitié Salpétrière, Service de Biochimie endocrinienne et Oncologique, Paris F-75013, France
Jacques Pariès, Department of Public health, Jean Verdier Hospital, AP-HP, Bondy 93140, France
Jenny Vaysse, Department of Biochemistry, Jean Verdier Hospital, AP-HP, Bondy 93140, France
Pierre Nahon, Jean-Claude Trinchet, Michel Beaugrand, Nathalie Ganne-Carrié, Department of Hepato-Gastroenterology, Jean Verdier Hospital, AP-HP, Bondy 93140, France; UPRES EA3409, University Paris 13, Paris F-75651, France
Audrey Miroglio, Antoine Kerjean, Jamel Chelly, Cochin Institut-INSERM-CNRS-University Paris 5-CHU Cochin, Paris 75014, France
Author contributions: Ganne-Carrié N, Trinchet JC, Carrié A and Beaugrand M designed research; Nahon P selected patients; Pariès J analyzed data; Vaysse J tested IGF2 serum level; Couvert P, Kerjean A, Miroglio A and Chelly J performed molecular analyses; Couvert P and Ganne-Carrié N wrote the paper.
Correspondence to: Dr. Nathalie Ganne-Carrié, Department of Hepato-Gastroenterology, Jean Verdier Hospital, AP-HP, Bondy 93140, France. nathalie.ganne@jvr.aphp.fr
Telephone: +33-1-48026296 Fax: +33-1-48026202
Received: May 23, 2008 Revised: July 14, 2008 Accepted: July 21, 2008 Published online: September 21, 2008
Abstract
AIM: To assess the predictive value of the insulin-like growth factor 2 (Igf2) methylation profile for the occurrence of Hepatocellular Carcinoma (HCC) in hepatitis C (HCV) cirrhosis.
METHODS: Patients with: (1) biopsy-proven compensated HCV cirrhosis; (2) available baseline frozen liver sample; (3) absence of detectable HCC; (4) regular screening for HCC; (5) informed consent for genetic analysis were studied. After DNA extraction from liver samples and bisulfite treatment, unbiased PCR and DHPLC analysis were performed for methylation analysis at the Igf2 locus. The predictive value of the Igf2 methylation profile for HCC was assessed by Kaplan-Meier and Cox methods.
RESULTS: Among 94 included patients, 20 developed an HCC during follow-up (6.9 ± 3.2 years). The methylation profile was hypomethylated, intermediate and hypermethylated in 13, 64 and 17 cases, respectively. In univariate analysis, two baseline parameters were associated with the occurrence of HCC: age (P = 0.01) and prothrombin (P = 0.04). The test of linear tendency between the three ordered levels of Igf2 methylation and probability of HCC occurrence was significant (Log Rank, P = 0.043; Breslow, P = 0.037; Tarone-Ware, P = 0.039).
CONCLUSION: These results suggest that hypome-thylation at the Igf2 locus in the liver could be predictive for HCC occurrence in HCV cirrhosis.
