Genome-wide DNA methylation profiling during metabolic dysfunction-associated steatohepatitis-related hepatocarcinogenesis - Original research

Sep 22, 2026

This study compares ethnicity-related differences in DNA methylation profiles during metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocarcinogenesis in patients from Japan and the United States. Genome-wide DNA methylation analysis using the Infinium assay was performed on 36 normal liver tissue, 148 non-cancerous MASH, and 36 MASH-related hepatocellular carcinoma samples (220 total) from both cohorts. Principal component analysis showed distinct MASH methylation signatures and cohort-specific differences, with cancer gene alterations in MASH inherited or strengthened in MASH-related HCC, affecting gene expression.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Study purpose and design

Cohorts and methylation profiling

Analytical findings (PCA, shared and cohort-specific genes)

Biological interpretation and implications

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Genome-wide DNA methylation profiling during metabolic dysfunction-associated steatohepatitis-related hepatocarcinogenesis in patients in Japan and the United States Junko Kuramoto1􀀍, Eri Arai1, Mao Fujimoto1, Hiroki Muramoto1, Hidenori Ojima2, Yosuke Seki3, Kazunori Kasama3, Nobuaki Funahashi4, Haruhide Udagawa5, Takao Nammo6,7, Kazuki Yasuda8,9, Nobuyoshi Hiraoka10, Teruhiko Yoshida11, Kimberley Jane Evason12 & Yae Kanai1 This study aimed to compare ethnicity-related differences in DNA methylation profiles during metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocarcinogenesis in patients from Japan and the United States (US) . Genome-wide DNA methylation analysis using the Infiniumassay was performed in 36, 148 and 36 samples of normal liver tissue (NLT), non-cancerous liver tissue showing MASH, and MASH-related hepatocellular carcinoma (HCC), respectively (220 samples in total), from the Japan and US cohorts. Principal component analysis revealed that MASH had a distinct DNA methylation profile differing from that of NLT, and that the MASH profiles in the two cohorts differed from each other. DNA methylation alterations of cancer-related genes in MASH were inherited by or strengthened in MASH-related HCC itself, resulting in expression alterations. DNA methylation alterations ofFGFR2, FUT4, B3GNT5 and MOSC1 in the precancerous MASH stage were shared by the two cohorts, suggesting that such genes are commonly associated with MASH-related hepatocarcinogenesis. On the other hand, it was suggested that DNA methylation alterations of ZNF611 and SAMD10, and those of SHC1, are involved specifically in MASH-related hepatocarcinogenesis in the Japan and the US cohorts, respectively. These findings suggest that DNA methylation alterations, which may reflect race and lifestyle, are associated with MASH-related hepatocarcinogenesis. Keywords Genome-wide DNA methylation analysis, Metabolic dysfunction-associated steatohepatitis, Hepatocellular carcinoma, Japan, The United States Abbreviations 1Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo 160-8582, Japan. 2Division of Molecular Pathology, Tochigi Cancer Center, Utsunomiya 320-0834, Japan. 3Weight Loss and Metabolic Surgery Center, Yotsuya Medical Cube, Tokyo 102-0084, Japan. 4School of Life Science and Technology, Institute of Science Tokyo,Yokohama 226-8501, Japan. 5Department of Registered Dietitians, Faculty of Health and Nutrition, Bunkyo University, Chigasaki 253-8550, Japan. 6Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. 7Department of Internal Medicine, Gratia Hospital, Osaka 562-8567, Japan. 8Department of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo 181-8611, Japan. 9Diabetes Research Center, Japan Institute for Health Security, Tokyo 162-8655, Japan. 10Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo 104-0045, Japan. 11Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo 104-0045, Japan. 12Department of Pathology, and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. 􀀍 email: [j-kuramoto@keio.jp](j-kuramoto@keio.jp) AUC Area under the curve 5-aza-dC 5-Aza-2'-deoxycytidine CT Cycle threshold FDR False discovery rate HBV Hepatitis B virus HCC Hepatocellular carcinoma HCV Hepatitis C virus JCRB Japanese Collection of Research Bioresources J-MASH-O Non-cancerous liver tissue showing metabolic dysfunction-associated steatohepatitis from patients without hepatocellular carcinoma in Japan J-MASH-W Non-cancerous liver tissue showing metabolic dysfunction-associated steatohepatitis from patients with hepatocellular carcinoma in Japan J-MASH-T Metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma f

FAQs

How were DNA methylation profiles measured in this study?

Genome-wide DNA methylation analysis was performed using the Infinium assay across normal liver tissue, non-cancerous MASH tissue, and MASH-related hepatocellular carcinoma samples.

What sample groups were included, and how many samples were analyzed?

The study analyzed 36 normal liver tissue samples, 148 non-cancerous MASH samples, and 36 MASH-related hepatocellular carcinoma samples, totaling 220 samples from Japan and the US cohorts.

What did principal component analysis show about MASH and cohort differences?

MASH showed a distinct DNA methylation profile compared with normal liver tissue, and methylation profiles differed between the Japanese and US cohorts.

Sep 22, 2026

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