Evidence map›Paper›PMID 41105505›Full record

ArticleUnited European gastroenterology journal2025

Cell-Free DNA Methylation-Based Liquid Biopsy Assay to Identify Lymph Node Metastasis in T1 Gastric Cancer.

Keisuke Okuno, Adwait Joshi, Shuichi Watanabe, Sakiko Oba, Kenta Yao, Toshiro Tanioka, Masanori Tokunaga, Daisuke Ban, Yusuke Kinugasa

Abstract read
In one paragraph

Article in United European gastroenterology journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

2 citing papers in PubMed.

  1. Review
  2. Article
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

9 authors.

Keisuke OkunoDepartment of Gastrointestinal Surgery, Institute of Science Tokyo, Tokyo, Japan.ORCID https://orcid.org/0009-0009-6964-2726
Adwait JoshiImperial College School of Medicine, London, UK.
Shuichi WatanabeDivision of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.
Sakiko ObaDepartment of Gastrointestinal Surgery, Institute of Science Tokyo, Tokyo, Japan.
Kenta YaoDepartment of Gastrointestinal Surgery, Institute of Science Tokyo, Tokyo, Japan.
Toshiro TaniokaDepartment of Gastrointestinal Surgery, Institute of Science Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0001-8142-4750
Masanori TokunagaDepartment of Gastrointestinal Surgery, Institute of Science Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0002-3183-349X
Daisuke BanDepartment of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0003-0868-8519
Yusuke KinugasaDepartment of Gastrointestinal Surgery, Institute of Science Tokyo, Tokyo, Japan.

Funding

Japan Society for the Promotion of Science JP23K19499Japan Society for the Promotion of Science JP24K18571Kobayashi Foundation for Cancer Research 2023DI008
6 · The paper itself

Abstract

backgroundMost T1 gastric cancer (GC) harbor lymph node metastasis (LNM) at a rate of < 20%; however, owing to the difficulty in accurately diagnosing LNM preoperatively, many patients with T1 GC undergo unnecessary invasive radical gastrectomy with lymphadenectomy. In the present study, we established an epigenetic liquid biopsy assay for the preoperative diagnosis of LNM in T1 GC.

methodsA comprehensive biomarker discovery was performed by analyzing genome-wide DNA methylation profiling. We obtained 277 clinical specimens, including 177 surgical tissues and 100 pre-operative plasmas. DNA methylation biomarkers were trained and validated using quantitative methylation-specific polymerase chain reaction (qMSP) assays.

resultsWe identified six novel differentially methylated regions, including at least two differentially methylated CpG probes (|Delta-beta| > 0.12 and p < 0.05) within 100 bp, through genome-wide biomarker discovery. A DNA methylation panel was generated using qMSP assays in clinical tissue specimens, with an area under the curve (AUC) of 0.80. This panel was validated in an independent clinical cohort, and a combined model, which integrated the DNA methylation model with preoperative computed tomography -based findings, was established through multivariate logistic regression analyses (AUC: 0.84). Finally, we translated this model into a liquid biopsy, and this cell-free DNA (cfDNA) methylation model exhibited robust performance for LNM identification in T1 GC (AUC: 0.86) and allowed 44% of patients to avoid unnecessary invasive operations, without missing any LNM-positive patients.

conclusionsWe have successfully developed a cfDNA methylation signature-based liquid biopsy diagnostic assay that allows for robust and less-invasive LNM detection in patients with T1 GC.

Indexed as

Biomarkers, TumorCell-Free Nucleic AcidsDNA MethylationLymphatic MetastasisStomach NeoplasmsAgedCpG IslandsFemaleGastrectomyHumansLiquid BiopsyLymph Node ExcisionLymph NodesMaleMiddle AgedNeoplasm StagingBiomarkers, TumorCell-Free Nucleic Acidscell‐free DNADNA methylationliquid biopsylymph node metastasisT1 gastric cancer

Identifiers

PMID41105505
PMCPMC12704565

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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.