DNA Methylation in Noncancerous Liver Tissues as Biomarker for Multicentric Occurrence of Hepatitis C Virus-Related Hepatocellular Carcinoma.

Content Provider	Europe PMC
Author	Suzuki, Hiroyuki Iwamoto, Hideki Yamamoto, Ken Tsukaguchi, Mai Nakamura, Toru Masuda, Atsutaka Sakaue, Takahiko Tanaka, Toshimitsu Niizeki, Takashi Okamura, Shusuke Shimose, Shigeo Shirono, Tomotake Noda, Yu Kamachi, Naoki Kuromatsu, Ryoko Hisaka, Toru Yano, Hirohisa Koga, Hironori Torimura, Takuji
Copyright Year	2022
Abstract	Background and AimsHepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) progresses with a highly multicentric occurrence (MO) even after radical hepatectomy. Despite several efforts to clarify the pathogenesis of MO, the underlying molecular mechanism remains elusive. The aim of this study was to evaluate alterations in DNA methylation in noncancerous liver tissues in the MO of HCC.MethodsA total of 203 patients with HCV-related HCC who underwent radical hepatectomy at our hospital between January 2008 and January 2012 were recruited. We defined a group of nonearly recurrence of HCC (NR) for ≥3 years after radical hepatectomy and a group of early recurrence of HCC (ER) with MO within 2 years after radical hepatectomy.ResultsThree patients each were selected in the NR and ER groups in the first set, and 13 patients in the NR group and 17 patients in the ER group were selected in the second set. Genome-wide DNA methylation profiles were obtained from noncancerous liver tissues using a Human Methylation 450 BeadChip, and the differences between the groups were analyzed for each set. After excluding single nucleotide polymorphism-associated methylation sites and low-call sites, 401,282 sites were assessed using a generalized linear model without any adjustments. Nine gene regions, APBB1P, CLSTN3, DLG5, IRX5, OAS1, SOX12, SNX19, TENM2, and TRIM54, exhibiting a significant difference (P < .001) in DNA methylation levels were identified in the common direction between the 2 analysis sets.ConclusionAlterations in DNA methylation of 9 genes in noncancerous liver tissues appear to be involved in MO after radical hepatectomy for HCV-related HCC.
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Volume Number	1
DOI	10.1016/j.gastha.2022.02.016
PubMed Central reference number	PMC11307517
Issue Number	4
PubMed reference number	39132059
Journal	Gastro Hep Advances [Gastro Hep Adv]
e-ISSN	27725723
Language	English
Publisher	Elsevier
Publisher Date	2022-05-06
Access Restriction	Open
Rights License	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). © 2022 The Authors
Subject Keyword	Hepatocellular Carcinoma DNA Methylation Hepatitis C Virus Multicentric Occurrence
Content Type	Text
Resource Type	Article
Subject	Medicine