Liver insulin-like growth factor 2 methylation in hepatitis C virus cirrhosis and further occurrence of hepatocellular carcinoma

Couvert, Philippe; Carrié, Alain; Pariès, J.; Vaysse, J; Miroglio, Audrey; Kerjean, Antoine; Nahon, Pierre; Chelly, Jamel; Trinchet, Jean–Claude; Beaugrand, Michel; Ganne-Carrié, Nathalie

doi:10.3748/wjg.14.5419

Cited by 22 publications

(15 citation statements)

References 55 publications

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“…(Table 1) The candidate sites include genes related to growth factors, growth factor receptors, cytokines/chemokines, cytokine/chemokine receptors, apoptosis, tumor suppression, DNA repair, cell‐cycle regulation, metabolism, cell–cell interaction, and chromosome segregation. Most of them have been reported to be associated with carcinogenesis as well as HCC susceptibility 8–30 . SNPs of the selected genes were extracted from the Japanese Single Nucleotide Polymorphisms database (http://snp.ims.u-tokyo.ac.jp), a database for SNPs found in the Japanese population, and from National Center for Biotechnology Information.…”

Section: Methodsmentioning

confidence: 99%

Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: A case control study

Tomoda¹,

Nouso²,

Sakai³

et al. 2012

J of Gastro and Hepatol

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Backgroud and Aim: Chronic hepatitis C virus (HCV) infection is a well known risk factor for hepatocellular carcinoma (HCC). The aim of this study is to elucidate the genetic risk of development and recurrence of HCC in patients with HCV. Methods: A total of 468 patients with HCV, including 265 with HCC were enrolled. We genotyped 88 single nucleotide polymorphisms (SNPs) in 81 genes expected to influence hepatocarcinogenesis using the iPLEX assay. Risk of HCC was clarified by stratifying patients into risk groups based on the multiplied odds ratio (MOR) for SNPs associated with HCC, and the cumulative effects on the development and recurrence of HCC were analyzed. Results: Six SNPs associated with risk of HCC were identified (OR range: 0.29–1.76). These included novel SNPs for hepatocarcinogenesis with HCV CCND2 rs1049606, RAD23B rs1805329, CEP164 rs573455, and GRP78rs430397 in addition to the known SNPs MDM2 rs2279744 and ALDH2 rs671. MOR analysis revealed that the highest risk group exerted about a 19‐fold higher relative OR compared with the lowest risk group (P = 1.08 × 10−5). Predicted 10‐year HCC risk ranged from 1.7% to 96% depending on the risk group and the extent of fibrosis. Recurrence‐free survival of radiofrequency ablation‐treated HCC in the high risk group (n = 53) was lower than that of low risk group (n = 58, P = 0.038). Conclusion: Single nucleotide polymorphisms of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of HCC in Japanese patients with HCV.

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Section: Methodsmentioning

confidence: 99%

Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: A case control study

Tomoda¹,

Nouso²,

Sakai³

et al. 2012

J of Gastro and Hepatol

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“…HCV-induced ROS have been shown to activate histone deacetylase in a fashion similar to hydrogen peroxide and to cause hypoacetylation of histones [149]. Hypomethylation of the IGF-2 locus in hepatitis C cirrhosis has been shown to predict HCC development [150]. Another study reported the hypermethylation of p16, p15, p14, pRB and the PTEN promoters in patients with sustained viral response in comparison to non-responders [151].…”

Section: Genetic and Epigenetic Changes In Hcv-induced Hepato-carcinomentioning

confidence: 97%

Hepatitis C virus-induced hepatocarcinogenesis

Bartosch¹,

Thimme²,

Blum³

et al. 2009

Journal of Hepatology

140

108

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Although there is strong evidence that hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma (HCC), there is still much to understand regarding the mechanism of HCV-induced transformation. While liver fibrosis resulting from long-lasting chronic inflammation and liver regeneration resulting from immune-mediated cell death are likely factors that contribute to the development of HCC, the direct role of HCV proteins remains to be determined. In vitro studies have shown that HCV expression may interfere with cellular functions that are important for cell differentiation and cell growth. However, most studies were performed in artificial models which can only give clues for potential mechanisms that need to be confirmed in more relevant models. Furthermore, the difficulty to identify HCV proteins and infected liver cells in patients, contributes to the complexity of our current understanding. For these reasons, there is currently very little experimental evidence for a direct oncogenic role of HCV. Further studies are warranted to clarify these issues.

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“…6,7 Insulin-like growth factor-II (IGF-II) is a mitogenic polypeptide closely related to insulin, and its gene has a complex transcription regulation that results in multiple mRNA transcripts by different promoters. 8,9 IGF-II is a kind of fetal growth factor but is also highly expressed during hepatocarcinogenesis, 10,11 and its reexpression has recently been described in HCC. 12,13 Although hepatic arterial embolization is widely used as an effective treatment of HCC on the basis of hypervascularization, IGF-II substantially increases vascular endothelial growth factor expression in a time-dependent manner in hepatoma cells.…”

mentioning

confidence: 99%

Characteristics of Hepatic IGF-II Expression and Monitored Levels of Circulating IGF-II mRNA in Metastasis of Hepatocellular Carcinoma

Qian

Yao

Dong

et al. 2010

American Journal of Clinical Pathology

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The prognosis of hepatocellular carcinoma (HCC) remains dismal. Insulin-like growth factor II (IGF-II), a fetal growth factor, is highly expressed during HCC development. We examined serum IGF-II levels and circulating IGF-II messenger RNA (mRNA) expression and analyzed the clinicopathologic characteristics in patients with liver diseases. The higher IGF-II level in the serum of patients with HCC could be correlated with hepatitis B virus infection but not with patient sex, age, tumor size, or α-fetoprotein (AFP) level. Total RNAs were extracted from liver tissues or peripheral blood mononuclear cells, and IGF-II complementary DNA (cDNA) and AFP cDNA were synthesized through random primers and reverse transcriptase; gene fragments were amplified by nested polymerase chain reaction and confirmed by sequencing. The incidence of the hepatic IGF-II gene was 100% in HCC, 54.3% in paracancerous tissues, and none in noncancerous tissues. The incidence rates for circulating IGF-II and AFP genes were 34.3% and 52.7%, respectively, and for both, 61.6% in patients with HCC. They were 100% in cases with extrahepatic metastasis. The IGF-II abnormality associates with HCC, and circulating IGF-II and IGF-II mRNA are useful molecular markers for HCC differential diagnosis and hematogenous metastasis.

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Liver insulin-like growth factor 2 methylation in hepatitis C virus cirrhosis and further occurrence of hepatocellular carcinoma

Cited by 22 publications

References 55 publications

Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: A case control study

Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: A case control study

Hepatitis C virus-induced hepatocarcinogenesis

Characteristics of Hepatic IGF-II Expression and Monitored Levels of Circulating IGF-II mRNA in Metastasis of Hepatocellular Carcinoma

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