The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma
Open accessAbstract
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.
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1 retracted
Lysyl oxidase is essential for hypoxia-induced metastasis
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Focal Gains of VEGFA and Molecular Classification of Hepatocellular Carcinoma
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Steelman, L. S., Chappell, W. H., Abrams, S. L., Kempf, C. R., Long, J., Laidler, P., Mijatovic, S., Maksimovic-Ivanic, D., Stivala, F., Mazzarino, M. C., et al. (2011) · Aging · doi:10.18632/aging.100296 · Cited by 553
Mitochondrial Dysfunction in Cancer
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Self-citation
Metadata
- Authors
- Calvisi, D. F., Ladu, S., Gorden, A., Farina, M., Lee, J.-S., Conner, E. A., Schroeder, I., Factor, V. M., & Thorgeirsson, S. S.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-09-04
- Volume
- 117
- Issue
- 9
- Pages
- 2713-2722
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2114973741
- Cited by
- 393
- References
- 72
- FWCI
- 11.02
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Calvisi, D. F., Ladu, S., Gorden, A., Farina, M., Lee, J.-S., Conner, E. A., Schroeder, I., Factor, V. M., & Thorgeirsson, S. S. (2007). Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma. Journal of Clinical Investigation. https://doi.org/10.1172/jci31457
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