EphA2 on urinary extracellular vesicles as a novel biomarker for bladder cancer diagnosis and its effect on the invasiveness of bladder cancer.

Biomarkers / metabolism Ephrins / metabolism Extracellular Vesicles / metabolism Hematuria Humans Receptor, EphA2 Urinary Bladder Neoplasms / diagnosis

Journal

British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635

Informations de publication

Date de publication:
10 2022
Historique:
received: 02 12 2021
accepted: 11 05 2022
revised: 25 04 2022
pubmed: 7 7 2022
medline: 1 10 2022
entrez: 6 7 2022
Statut: ppublish

Résumé

Urinary extracellular vesicles (uEVs) secreted from bladder cancer contain cancer-specific proteins that are potential diagnostic biomarkers. We identified and evaluated a uEV-based protein biomarker for bladder cancer diagnosis and analysed its functions. Biomarker candidates, selected by shotgun proteomics, were validated using targeted proteomics of uEVs obtained from 49 patients with and 48 individuals without bladder cancer, including patients with non-malignant haematuria. We developed an enzyme-linked immunosorbent assay (ELISA) for quantifying the uEV protein biomarker without ultracentrifugation and evaluated urine samples from 36 patients with and 36 patients without bladder cancer. Thirteen membrane proteins were significantly upregulated in the uEVs from patients with bladder cancer in shotgun proteomics. Among them, eight proteins were validated by target proteomics, and Ephrin type-A receptor 2 (EphA2) was the only protein significantly upregulated in the uEVs of patients with bladder cancer, compared with that of patients with non-malignant haematuria. The EV-EphA2-CD9 ELISA demonstrated good diagnostic performance (sensitivity: 61.1%, specificity: 97.2%). We showed that EphA2 promotes proliferation, invasion and migration and EV-EphA2 promotes the invasion and migration of bladder cancer cells. We established EV-EphA2-CD9 ELISA for uEV-EphA2 detection for the non-invasive early clinical diagnosis of bladder cancer.

Sections du résumé

BACKGROUND
Urinary extracellular vesicles (uEVs) secreted from bladder cancer contain cancer-specific proteins that are potential diagnostic biomarkers. We identified and evaluated a uEV-based protein biomarker for bladder cancer diagnosis and analysed its functions.
METHODS
Biomarker candidates, selected by shotgun proteomics, were validated using targeted proteomics of uEVs obtained from 49 patients with and 48 individuals without bladder cancer, including patients with non-malignant haematuria. We developed an enzyme-linked immunosorbent assay (ELISA) for quantifying the uEV protein biomarker without ultracentrifugation and evaluated urine samples from 36 patients with and 36 patients without bladder cancer.
RESULTS
Thirteen membrane proteins were significantly upregulated in the uEVs from patients with bladder cancer in shotgun proteomics. Among them, eight proteins were validated by target proteomics, and Ephrin type-A receptor 2 (EphA2) was the only protein significantly upregulated in the uEVs of patients with bladder cancer, compared with that of patients with non-malignant haematuria. The EV-EphA2-CD9 ELISA demonstrated good diagnostic performance (sensitivity: 61.1%, specificity: 97.2%). We showed that EphA2 promotes proliferation, invasion and migration and EV-EphA2 promotes the invasion and migration of bladder cancer cells.
CONCLUSIONS
We established EV-EphA2-CD9 ELISA for uEV-EphA2 detection for the non-invasive early clinical diagnosis of bladder cancer.

Identifiants

DOI: 10.1038/s41416-022-01860-0 PMID: 35794239 PMC: PMC9519556
pubmed: 35794239
doi: 10.1038/s41416-022-01860-0
pii: 10.1038/s41416-022-01860-0
pmc: PMC9519556
doi:

Substances chimiques

Biomarkers 0
EPHA2 protein, human 0
Ephrins 0
Receptor, EphA2 EC 2.7.10.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1312-1323

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Eisuke Tomiyama (E)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.
ORCID: 0000-0002-0056-9446

Kazutoshi Fujita (K)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan. kfujita@med.kindai.ac.jp.
Department of Urology, Kindai University Faculty of Medicine, Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan. kfujita@med.kindai.ac.jp.
ORCID: 0000-0002-6774-7497

Kyosuke Matsuzaki (K)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Ryohei Narumi (R)

Laboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.

Akinaru Yamamoto (A)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Toshihiro Uemura (T)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Gaku Yamamichi (G)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Yoko Koh (Y)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Makoto Matsushita (M)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Yujiro Hayashi (Y)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Mamoru Hashimoto (M)

Department of Urology, Kindai University Faculty of Medicine, Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.

Eri Banno (E)

Department of Urology, Kindai University Faculty of Medicine, Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.

Taigo Kato (T)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Koji Hatano (K)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Atsunari Kawashima (A)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.
ORCID: 0000-0001-9369-4264

Motohide Uemura (M)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Ryo Ukekawa (R)

FUJIFILM Wako Pure Chemical Corporation, Takata-cho, Amagasaki, Hyogo, 661-0963, Japan.

Tetsuya Takao (T)

Department of Urology, Osaka General Medical Center, Bandai-higashi, Sumiyoshi-ku, Osaka, 558-8558, Japan.

Shingo Takada (S)

Department of Urology, Osaka Police Hospital, Kitayama-cho, Tennoji-ku, Osaka, 543-0035, Japan.

Hirotsugu Uemura (H)

Department of Urology, Kindai University Faculty of Medicine, Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.

Jun Adachi (J)

Laboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.
ORCID: 0000-0003-1220-3246

Takeshi Tomonaga (T)

Laboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan.

Norio Nonomura (N)

Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, 565-0871, Japan.
ORCID: 0000-0002-6522-6233

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › EphA2 on urinary extracellular vesicles as a...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Éphrines › EphA2 on urinary extracellular vesicles as a...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace extracellulaire › Vésicules extracellulaires › EphA2 on urinary extracellular vesicles as a...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Hémorragie › Hématurie › EphA2 on urinary extracellular vesicles as a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › EphA2 on urinary extracellular vesicles as a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs à activité tyrosine kinase › Famille des récepteurs Eph › Récepteur EphA2 › EphA2 on urinary extracellular vesicles as a...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs de la vessie urinaire › EphA2 on urinary extracellular vesicles as a...