Evidence map›Paper›PMID 36471401›Full record

ArticleClinical epigenetics2022

Quantification of DNA methylation for carcinogenic risk estimation in patients with non-alcoholic steatohepatitis.

Junko Kuramoto, Eri Arai, Mao Fujimoto, Ying Tian, Yuriko Yamada, Takuya Yotani, Satomi Makiuchi, Noboru Tsuda, Hidenori Ojima, Moto Fukai and 9 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Molecular mechanisms in MASLD/MASH-related HCC.Hepatology (Baltimore, Md.) · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 8 institutions in 1 country.

Junko KuramotoDepartment of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Eri AraiDepartment of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan. earai@keio.jp.
Mao FujimotoDepartment of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Ying TianDepartment of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Yuriko YamadaTsukuba Research Institute, Research and Development Division, Sekisui Medical Co., Ltd., Ryugasaki, 301-0852, Japan.
Takuya YotaniTsukuba Research Institute, Research and Development Division, Sekisui Medical Co., Ltd., Ryugasaki, 301-0852, Japan.
Satomi MakiuchiDepartment of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Noboru TsudaDepartment of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Hidenori OjimaDepartment of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Moto FukaiDepartment of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
Yosuke SekiWeight Loss and Metabolic Surgery Center, Yotsuya Medical Cube, Tokyo, 102-0084, Japan.
Kazunori KasamaWeight Loss and Metabolic Surgery Center, Yotsuya Medical Cube, Tokyo, 102-0084, Japan.
Nobuaki FunahashiDepartment of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan.
Haruhide UdagawaDepartment of Biochemistry, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
Takao NammoDepartment of Metabolic Medicine and Department of Diabetes Care Medicine, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.
Kazuki YasudaDepartment of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
Akinobu TaketomiDepartment of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
Tatsuya KantoThe Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan.
Yae KanaiDepartment of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Keio University Hospital · JPHokkaido University · JPKyorin University · JPSekisui Medical (Japan) · JPYotsuya Medical Cube · JPNational Center for Global Health and Medicine · JPOsaka University · JPTokyo Institute of Technology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn recent years, non-alcoholic steatohepatitis (NASH) has become the main cause of hepatocellular carcinoma (HCC). As a means of improving the treatment of NASH-related HCCs based on early detection, this study investigated the feasibility of carcinogenic risk estimation in patients with NASH.

resultsNormal liver tissue (NLT), non-cancerous liver tissue showing histological findings compatible with non-alcoholic fatty liver from patients without HCC (NAFL-O), non-cancerous liver tissue showing NASH from patients without HCC (NASH-O), non-cancerous liver tissue showing non-alcoholic fatty liver from patients with HCC (NAFL-W), non-cancerous liver tissue showing NASH from patients with HCC (NASH-W) and NASH-related HCC were analyzed. An initial cohort of 171 tissue samples and a validation cohort of 55 tissue samples were used. Genome-wide DNA methylation screening using the Infinium HumanMethylation450 BeadChip and DNA methylation quantification using high-performance liquid chromatography (HPLC) with a newly developed anion-exchange column were performed. Based on the Infinium assay, 4050 CpG sites showed alterations of DNA methylation in NASH-W samples relative to NLT samples. Such alterations at the precancerous NASH stage were inherited by or strengthened in HCC samples. Receiver operating characteristic curve analysis identified 415 CpG sites discriminating NASH-W from NLT samples with area under the curve values of more than 0.95. Among them, we focused on 21 CpG sites showing more than 85% specificity, even for discrimination of NASH-W from NASH-O samples. The DNA methylation status of these 21 CpG sites was able to predict the coincidence of HCC independently from histopathological findings such as ballooning and fibrosis stage. The methylation status of 5 candidate marker CpG sites was assessed using a HPLC-based system, and for 3 of them sufficient sensitivity and specificity were successfully validated in the validation cohort. By combining these 3 CpG sites including the ZC3H3 gene, NAFL-W and NASH-W samples from which HCCs had already arisen were confirmed to show carcinogenic risk with 95% sensitivity in the validation cohort.

conclusionsAfter a further prospective validation study using a larger cohort, carcinogenic risk estimation in liver biopsy specimens of patients with NASH may become clinically applicable using this HPLC-based system for quantification of DNA methylation.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsNon-alcoholic Fatty Liver DiseaseCarcinogenesisCarcinogensDNA MethylationHumansCarcinogensCarcinogenic risk estimationDNA methylationHepatocellular carcinomaHigh-performance liquid chromatographyInfinium assayNon-alcoholic steatohepatitis

Identifiers

PMID36471401
PMCPMC9724255
OpenAlexW4310777372

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.