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2015-06

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/110932

DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma

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https://doi.org/10.1002/hep.27732

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Epigenetic deregulation has emerged as a driver in human malignancies. There is no clear understanding of the epigenetic alterations in hepatocellular carcinoma (HCC) and of the potential role of DNA methylation markers as prognostic biomarkers. Analysis of tumor tissue from 304 patients with HCC treated with surgical resection allowed us to generate a methylation-based prognostic signature using a training-validation scheme. Methylome profiling was done with the Illumina HumanMethylation450 array (Illumina, Inc., San Diego, CA), which covers 96% of known cytosine-phosphate-guanine (CpG) islands and 485,000 CpG, and transcriptome profiling was performed with Affymetrix Human Genome U219 Plate (Affymetrix, Inc., Santa Clara, CA) and miRNA Chip 2.0. Random survival forests enabled us to generate a methylation signature based on 36 methylation probes. We computed a risk score of mortality for each individual that accurately discriminated patient survival both in the training (221 patients; 47% hepatitis C-related HCC) and validation sets (n = 83; 47% alcohol-related HCC). This signature correlated with known predictors of poor outcome and retained independent prognostic capacity of survival along with multinodularity and platelet count. The subset of patients identified by this signature was enriched in the molecular subclass of proliferation with progenitor cell features. The study confirmed a high prevalence of genes known to be deregulated by aberrant methylation in HCC (e.g., Ras association [RalGDS/AF-6] domain family member 1, insulin-like growth factor 2, and adenomatous polyposis coli) and other solid tumors (e.g., NOTCH3) and describes potential candidate epidrivers (e.g., septin 9 and ephrin B2). Conclusions: A validated signature of 36 DNA methylation markers accurately predicts poor survival in patients with HCC. Patients with this methylation profile harbor messenger RNA-based signatures indicating tumors with progenitor cell features.

Matèries

Càncer de fetge, Metilació, ADN, Epigènesi, Pronòstic mèdic

Matèries (anglès)

Liver cancer, Methylation, DNA, Epigenesis, Prognosis

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Articles publicats en revistes (Ciències Fisiològiques)
<b>Publicacions de projectes de recerca finançats per la UE</b>
Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
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VILLANUEVA, Augusto, PORTELA, Anna, SAYOLS, Sergi, BATTISTON, Carlo, HOSHIDA, Yujin, MÉNDEZ GONZÁLEZ, Jesús, IMBEAUD, Sandrine, LETOUZÉ, Eric, HERNÁNDEZ GEA, Virginia, CORNELLA, Helena, PINYOL, Roser, SOLÉ ARQUÉS, Manuel, FUSTER OBREGÓN, Josep, ZUCMAN-ROSSI, Jessica, MAZZAFERRO, Vincenzo, ESTELLER, Manel, LLOVET I BAYER, Josep maria, HEPTROMIC Consortium. DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma. _Hepatology_. 2015. Vol. 61, núm. 6, pàgs. 1945-1956. [consulta: 9 de gener de 2026]. ISSN: 0270-9139. [Disponible a: https://hdl.handle.net/2445/110932]

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