Evidence map›Paper›PMID 37186217›Full record

ArticleHepatology international2023

Methylated SEPT9 assay-based liquid biopsy as a biomarker in molecular targeted agent-treated hepatocellular carcinoma.

Issei Saeki, Yutaka Suehiro, Yurika Yamauchi, Tomomi Hoshida, Norikazu Tanabe, Takashi Oono, Daiki Kawamoto, Tatsuro Nishimura, Toshihiko Matsumoto, Tsuyoshi Ishikawa and 9 more

Abstract read
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In one paragraph

Article in Hepatology international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% 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

12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Diagnostic accuracy of methylatedFrontiers in endocrinology · 2025
    Pooled it
  3. Article
  4. Article
  5. Novel Liquid Biopsy in Gastrointestinal Cancers.Journal of gastroenterology and hepatology · 2026
    Review
  6. Review
  7. Review
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  9. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 1 country.

Issei SaekiDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Yutaka SuehiroDepartment of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Yurika YamauchiDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Tomomi HoshidaDepartment of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Norikazu TanabeDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Takashi OonoDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Daiki KawamotoDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Tatsuro NishimuraDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Toshihiko MatsumotoDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Tsuyoshi IshikawaDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Mototsugu ShimokawaDepartment of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Akihiro TamoriDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Abeno-ku, Osaka, 545-8585, Japan.
Norifumi KawadaDepartment of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Abeno-ku, Osaka, 545-8585, Japan.
Yasuyuki TamaiDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Tsu, Mie, 514-8507, Japan.
Motoh IwasaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Tsu, Mie, 514-8507, Japan.
Hayato NakagawaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Tsu, Mie, 514-8507, Japan.
Hiroaki NaganoDepartment of Gastroenterological, Breast, and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Taro TakamiDepartment of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan.
Takahiro YamasakiDepartment of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, 755-8505, Japan. t.yama@yamaguchi-u.ac.jp.ORCID http://orcid.org/0000-0002-9793-0399
Yamaguchi University · JPMie University · JPOsaka City University · JP

Funding

Japan Agency for Medical Research and Development 22ck0106627h0003Japan Society for the Promotion of Science 19K17463
6 · The paper itself

Abstract

backgroundThe development of molecular targeted agents (MTAs) has changed the treatment strategy for hepatocellular carcinoma (HCC). However, currently, there are no established predictive biomarkers for the treatment efficacy of MTAs. Previously, we developed a novel liquid biopsy test for HCC screening using sensitive methylated DNA testing of septin 9 gene (SEPT9). Here, we hypothesized that SEPT9 could be used as a biomarker for MTA treatment efficacy.

methodsWe enrolled 157 patients receiving sorafenib or lenvatinib as a first-line therapy and allocated 85 and 72 patients to the training and validation cohorts, respectively. For the methylation assay, DNA was treated with methylation-sensitive restriction enzymes, followed by multiplex droplet digital PCR. Various clinical parameters were compared with clinical outcomes.

resultsThe multivariate analysis revealed Eastern Cooperative Oncology Group performance status (≥ 1; p = 0.048), alpha-fetoprotein (AFP) (≥ 400 ng/mL; p < 0.001), and methylated-septin-9 (m-SEPT9) (≥ 205 copies/mL; p = 0.018) as significant predictors of poor overall survival (OS) in the training cohort. m-SEPT9 was identified as a predictor of poor OS in the validation cohort. We developed a predictive score, called the MTA score, consisting of these three significant OS parameters (two points were added for AFP and one point for each of the other predictors). Patients with MTA scores ≥ 2 showed a significantly poor prognosis compared to those with MTA scores ≤ 1 in both the training and validation cohorts.

conclusionsm-SEPT9 could be a potential predictive biomarker for survival in patients with HCC treated with MTAs.

Indexed as

Antineoplastic AgentsCarcinoma, HepatocellularLiver Neoplasmsalpha-FetoproteinsDNAHumansLiquid BiopsyMolecular Targeted TherapySeptinsalpha-FetoproteinsAntineoplastic AgentsDNASeptinsLenvatinibMethylated septin 9Predictive scorePrognosisSorafenib

Identifiers

PMID37186217
OpenAlexW4366982609

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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.