Evidence map›Paper›PMID 33441949›Full record

ArticleScientific reports2021

Utility of Claudin-3 in extracellular vesicles from human bile as biomarkers of cholangiocarcinoma.

Chisaki Ikeda, Hiroaki Haga, Naohiko Makino, Tatsutoshi Inuzuka, Ayako Kurimoto, Toshiki Ueda, Akiko Matsuda, Yasuharu Kakizaki, Tetsuya Ishizawa, Toshikazu Kobayashi and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

25 citing papers in PubMed, 30 citations in OpenAlex.

  1. Targeting claudins in cancer.Nature reviews. Drug discovery · 2026
    Review
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  3. Diagnostic and prognostic significance of circulating extracellular vesicles in gastrointestinal cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  9. Cholangiocarcinoma: The era of liquid biopsy.World journal of gastroenterology · 2025
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  12. Molecular Biomarkers in Cholangiocarcinoma: Focus on Bile.Current topics in medicinal chemistry · 2024
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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

14 authors at 1 institution in 1 country.

Chisaki IkedaDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
Hiroaki HagaDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan. hihaga@med.id.yamagata-u.ac.jp.
Naohiko MakinoDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
Tatsutoshi InuzukaH.U. Group Research Institute G.K., 51 Komiyamachi, Hachioji, Tokyo, 192-0031, Japan.
Ayako KurimotoH.U. Group Research Institute G.K., 51 Komiyamachi, Hachioji, Tokyo, 192-0031, Japan.
Toshiki UedaH.U. Group Research Institute G.K., 51 Komiyamachi, Hachioji, Tokyo, 192-0031, Japan.
Akiko MatsudaDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
Yasuharu KakizakiDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
Tetsuya IshizawaDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
Toshikazu KobayashiDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
Shinpei SugaharaDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
Michihiko TsunodaDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
Kensei SudaDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
Yoshiyuki UenoDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.
Yamagata University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Extracellular vesicles (EVs) are released from all cells. Bile directly contacts bile duct tumor; bile-derived EVs may contain high concentrations of cancer biomarkers. We performed a proteomic analysis of human bile-derived EVs and identified a novel biomarker of cholangiocarcinoma (CCA). EVs were isolated using ultracentrifugation, and chelating agents, ethylenediaminetetraacetic acid and ethylene glycol tetraacetic acid (EDEG) and phosphate buffered saline (PBS) were used as dissolution solutions. Bile was collected from 10 CCA and 10 choledocholithiasis (stones) cases. Proteomic analysis was performed; subsequently, ELISA was performed using the candidate biomarkers in a verification cohort. The vesicles isolated from bile had a typical size and morphology. The expression of exosome markers was observed. RNA was more abundant in the EDEG group. The proportion of microRNA was higher in the EDEG group. EDEG use resulted in the removal of more contaminants. Proteomic analysis identified 166 proteins as CCA-specific. ELISA for Claudin-3 revealed statistically significant difference. The diagnostic accuracy was AUC 0.945 and sensitivity and specificity were 87.5%. We report the first use of EDEG in the isolation of EVs from human bile and the proteomic analysis of human bile-derived EV-proteins in CCA. Claudin-3 in bile-derived EVs is a useful biomarker for CCA.

Indexed as

BileBile Duct NeoplasmsBile Ducts, IntrahepaticBiomarkers, TumorCholangiocarcinomaClaudin-3Extracellular VesiclesHumansMicroRNAsProteomicsBiomarkers, TumorClaudin-3MicroRNAs

Identifiers

PMID33441949
PMCPMC7807063
OpenAlexW3118788689

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LicenceCC BY
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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.