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Gastroenterology Research and Practice
Volume 2014 (2014), Article ID 597164, 9 pages
Research Article

Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials

1Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA
2Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA
3Laboratorio de Patología Molecular, Departamento de Anatomí a Patológica, CEGIN-BIOREN, Facultad de Medicina, Universidad de La Frontera, 4781176 Temuco, Chile
4Department of Gastroenterology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
5Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
6Bellvitge Biomedical Research Institute, Barcelona, Catalonia, Spain
7Department of Obstetrics and Gynecology, University of Puerto Rico School of Medicine, San Juan, PR 00927, USA

Received 3 December 2013; Revised 4 February 2014; Accepted 7 February 2014; Published 17 April 2014

Academic Editor: Ronghua Zhao

Copyright © 2014 Christina Michailidi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The majority of the epigenomic reports in hepatocellular carcinoma have focused on identifying novel differentially methylated drivers or passengers of the oncogenic process. Few reports have considered the technologies in place for clinical translation of newly identified biomarkers. The aim of this study was to identify epigenomic technologies that need only a small number of samples to discriminate HCC from non-HCC tissue, a basic requirement for biomarker development trials. To assess that potential, we used quantitative Methylation Specific PCR, oligonucleotide tiling arrays, and Methylation BeadChip assays. Concurrent global DNA hypomethylation, gene-specific hypermethylation, and chromatin alterations were observed as a hallmark of HCC. A global loss of promoter methylation was observed in HCC with the Illumina BeadChip assays and the Nimblegen oligonucleotide arrays. HCC samples had lower median methylation peak scores and a reduced number of significant promoter-wide methylated probes. Promoter hypermethylation of RASSF1A, SSBP2, and B4GALT1 quantified by qMSP had a sensitivity ranging from 38% to 52%, a specificity of 100%, and an AUC from 0.58 to 0.75. A panel combining these genes with HCC risk factors had a sensitivity of 87%, a specificity of 100%, and an AUC of 0.91.