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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
13 01 2021
Historique:
received: 26 08 2020
accepted: 30 12 2020
entrez: 14 1 2021
pubmed: 15 1 2021
medline: 17 8 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33441949
doi: 10.1038/s41598-021-81023-y
pii: 10.1038/s41598-021-81023-y
pmc: PMC7807063
doi:

Substances chimiques

Biomarkers, Tumor 0
Claudin-3 0
MicroRNAs 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1195

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Auteurs

Chisaki Ikeda (C)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.

Hiroaki Haga (H)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan. hihaga@med.id.yamagata-u.ac.jp.

Naohiko Makino (N)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.

Tatsutoshi Inuzuka (T)

H.U. Group Research Institute G.K., 51 Komiyamachi, Hachioji, Tokyo, 192-0031, Japan.

Ayako Kurimoto (A)

H.U. Group Research Institute G.K., 51 Komiyamachi, Hachioji, Tokyo, 192-0031, Japan.

Toshiki Ueda (T)

H.U. Group Research Institute G.K., 51 Komiyamachi, Hachioji, Tokyo, 192-0031, Japan.

Akiko Matsuda (A)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.

Yasuharu Kakizaki (Y)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.

Tetsuya Ishizawa (T)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.

Toshikazu Kobayashi (T)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.

Shinpei Sugahara (S)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.

Michihiko Tsunoda (M)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.

Kensei Suda (K)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.

Yoshiyuki Ueno (Y)

Department of Gastroenterology, Faculty of Medicine, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, 990-8595, Japan.

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Classifications MeSH