Insulin-like growth factor 2 gene methylation in peripheral blood mononuclear cells of patients with hepatitis C related cirrhosis or hepatocellular carcinoma

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• 作者：Philippe Couvert ; Alain Carri¨¦ ; Sophie Tezenas du Montcel ; Jenny Vaysse ; Angela Sutton ; Nathalie Barget ; Jean-Claude Trinchet ; Michel Beaugr ; Nathalie Ganne ; Philippe Giral ; Jamel Chelly
• 刊名：Clinics and Research in Hepatology and Gastroenterology
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：36
• 期：4
• 页码：345-351
• 全文大小：530 K

文摘

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Summary

Igf2 gene specific hypomethylation has been demonstrated in hepatocellular carcinoma (HCC) cells and in non-tumoral liver samples from patients with HCV-related cirrhosis who further developed HCC. In patients with colorectal cancers, Igf2 hypomethylation is found in peripheral blood mononuclear cells (PBMC) even prior to the occurrence of cancer.

Aim

To compare Igf2 methylation in PBMC from healthy donors and patients with HCV-related cirrhosis without or with history of HCC.

Patients and methods

After DNA extraction from frozen PBMC samples of 52 healthy blood donors and 121 patients with HCV-related cirrhosis either without (n = 59) or with past or present HCC (n = 62), and sodium bisulfite treatment, unbiased PCR amplification and Denaturing High Performance Liquid Chromatography (DHPLC) analysis were used for methylation analysis at the differentially methylated region 2 of Igf2. Methylation profiles were classified in three groups (unmethylated, U; methylated, M; and intermediate, UM) according to the proportions of M and U alleles, blindly to clinical data. In addition, 677C-T mutation of Methylenetetrahydrofolate Reductase (MTHFR) was investigated by fluorescent probes.

Results

Prevalences of U, UM and M Igf2 profiles were: 8 % , 65 % and 27 % in blood donors, 0 % , 81 % and 19 % in patients with HCV-related cirrhosis without HCC, 71 % , 29 % and 0 % in patients with HCC (P < 0.0001). Igf2 methylation profile was independent from gender, age, body mass index, and presence of 677C-T mutation of MTHFR.

Conclusion

These observations suggest a decrease of Igf2 methylation from cirrhosis to HCC in patients with HCV infection, which may be an additional risk factor for HCC.