Genome-wide and gene-specific epigenomic platforms for hepatocellular carcinoma biomarker development trials.
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.
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA.
Christina
C
Michailidi
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA.
Ethan
0000-0003-4846-7614
E
Soudry
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA.
Mariana
0000-0002-1652-8921
M
Brait
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA.
Leonel
0000-0002-2249-8511
L
Maldonado
Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA.
Andrew
A
Jaffe
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA ; Laboratorio de Patología Molecular, Departamento de Anatomí a Patológica, CEGIN-BIOREN, Facultad de Medicina, Universidad de La Frontera, 4781176 Temuco, Chile.
Carmen
C
Ili-Gangas
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA ; Laboratorio de Patología Molecular, Departamento de Anatomí a Patológica, CEGIN-BIOREN, Facultad de Medicina, Universidad de La Frontera, 4781176 Temuco, Chile.
Priscilla
P
Brebi-Mieville
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA.
Jimena
J
Perez
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA.
Myoung Sook
MS
Kim
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA.
Xiaoli
X
Zhong
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA.
Quiang
Q
Yang
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA.
Blanca
B
Valle
Department of Gastroenterology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA.
Stephen J
SJ
Meltzer
Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA.
Michael
M
Torbenson
Bellvitge Biomedical Research Institute, Barcelona, Catalonia, Spain.
Manel
M
Esteller
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA.
David
D
Sidransky
Department of Otolaryngology, Division of Head and Neck Cancer Research, School of Medicine, The Johns Hopkins University, Baltimore, MD 21231, USA ; Department of Obstetrics and Gynecology, University of Puerto Rico School of Medicine, San Juan, PR 00927, USA.
Rafael
R
Guerrero-Preston