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Citations to this article

Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma
Diego F. Calvisi, … , Valentina M. Factor, Snorri S. Thorgeirsson
Diego F. Calvisi, … , Valentina M. Factor, Snorri S. Thorgeirsson
Published September 4, 2007
Citation Information: J Clin Invest. 2007;117(9):2713-2722. https://doi.org/10.1172/JCI31457.
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Research Article Oncology Article has an altmetric score of 6

Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma

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Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, accounting for an estimated 600,000 deaths annually. Aberrant methylation, consisting of DNA hypomethylation and/or promoter gene CpG hypermethylation, is implicated in the development of a variety of solid tumors, including HCC. We analyzed the global levels of DNA methylation as well as the methylation status of 105 putative tumor suppressor genes and found that the extent of genome-wide hypomethylation and CpG hypermethylation correlates with biological features and clinical outcome of HCC patients. We identified activation of Ras and downstream Ras effectors (ERK, AKT, and RAL) due to epigenetic silencing of inhibitors of the Ras pathway in all HCC. Further, selective inactivation of SPRY1 and -2, DAB2, and SOCS4 and -5 genes and inhibitors of angiogenesis (BNIP3, BNIP3L, IGFBP3, and EGLN2) was associated with poor prognosis. Importantly, several epigenetically silenced putative tumor suppressor genes found in HCC were also inactivated in the nontumorous liver. Our results assign both therapeutic and chemopreventive significance to methylation patterns in human HCC and open the possibility of using molecular targets, including those identified in this study, to effectively inhibit HCC development and progression.

Authors

Diego F. Calvisi, Sara Ladu, Alexis Gorden, Miriam Farina, Ju-Seog Lee, Elizabeth A. Conner, Insa Schroeder, Valentina M. Factor, Snorri S. Thorgeirsson

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 2 6 6 13 16 8 15 6 8 12 9 19 15 13 11 19 7 8 193
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Citations to this article in year 2015 (9)

Title and authors Publication Year
Mitophagy defects arising from BNip3 loss promote mammary tumor progression to metastasis
AH Chourasia, K Tracy, C Frankenberger, ML Boland, MN Sharifi, LE Drake, JR Sachleben, JM Asara, JW Locasale, GS Karczmar, KF Macleod
EMBO reports 2015
Mitophagy and cancer
AH Chourasia, ML Boland, KF Macleod
Cancer & Metabolism 2015
Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival
ZS Niu
World journal of hepatology 2015
Epigenetic Regulation in Hepatocellular Carcinoma Requires Long Noncoding RNAs
L Amicone, F Citarella, C Cicchini
BioMed Research International 2015
Low Expression of LDHB Correlates With Unfavorable Survival in Hepatocellular Carcinoma: Strobe-Compliant Article
R Chen, X Zhou, Z Yu, J Liu, G Huang
Medicine 2015
SOCS3 Methylation Predicts a Poor Prognosis in HBV Infection-Related Hepatocellular Carcinoma
X Zhang, Q You, X Zhang, X Chen
International journal of molecular sciences 2015
Wnt-/-β-catenin pathway signaling in human hepatocellular carcinoma
J Waisberg
World journal of hepatology 2015
DNA methylation in hepatocellular carcinoma: what is the use?
J Dekervel, J van Pelt, C Verslype
Hepatic Oncology 2015
Chronic liver inflammation modifies DNA methylation at the precancerous stage of murine hepatocarcinogenesis
Stoyanov E, Ludwig G, Mizrahi L, Olam D, Schnitzer-Perlman T, Tasika E, Sass G, Tiegs G, Jiang Y, Nie T, Kohler J, Schinazi RF, Vertino PM, Cedar H, Galun E, Goldenberg D
Oncotarget 2015

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