Evidence map›Paper›PMID 33778046›Full record

ArticleERJ open research2021

Proteomics of serum extracellular vesicles identifies a novel COPD biomarker, fibulin-3 from elastic fibres.

Taro Koba, Yoshito Takeda, Ryohei Narumi, Takashi Shiromizu, Yosui Nojima, Mari Ito, Muneyoshi Kuroyama, Yu Futami, Takayuki Takimoto, Takanori Matsuki and 23 more

Open access · goldAbstract read
In one paragraph

Article in ERJ open research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 15% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. The dual promise of extracellular vesicles in lung diseases: towards reliable biomarkers and drug delivery vectors.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  5. Multi-omics to study chronic respiratory diseases and viral infections.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Signature Proteins in Small Extracellular Vesicles of Granulocytes and CD4International journal of molecular sciences · 2024
    Article
  12. Review
  13. Article
  14. Review
  15. Extracellular vesicles and COPD: foe or friend?Journal of nanobiotechnology · 2023
    Review
  16. Serum Proteomic Profiling in Patients with Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2023
    Article
  17. Article
  18. Article
  19. Article
  20. 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

33 authors at 5 institutions in 1 country.

Taro KobaDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.ORCID https://orcid.org/0000-0001-7715-9042
Yoshito TakedaDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Ryohei NarumiLaboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Takashi ShiromizuLaboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Yosui NojimaLaboratory of Bioinformatics, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.ORCID https://orcid.org/0000-0002-6821-0093
Mari ItoLaboratory of Bioinformatics, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Muneyoshi KuroyamaDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yu FutamiDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takayuki TakimotoDept of Respiratory Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Kita-Ku, Sakai, Osaka, Japan.
Takanori MatsukiDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Ryuya EdahiroDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Satoshi NojimaDept of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yoshitomo HayamaDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kiyoharu FukushimaDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Haruhiko HirataDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Shohei KoyamaDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kota IwahoriDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Izumi NagatomoDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Mayumi SuzukiDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yuya ShiraiDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Teruaki MurakamiDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kaori NakanishiDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.ORCID https://orcid.org/0000-0002-4153-5277
Takeshi NakataniDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yasuhiko SugaDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kotaro MiyakeDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takayuki ShiroyamaDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Hiroshi KidaDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.ORCID https://orcid.org/0000-0002-9351-7855
Takako SasakiDept of Biochemistry II, Faculty of Medicine, Oita University, Yufu, Oita, Japan.
Koji UedaCancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Koto, Tokyo, Japan.
Kenji MizuguchiLaboratory of Bioinformatics, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Jun AdachiLaboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Takeshi TomonagaLaboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Atsushi KumanogohDept of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
The University of Osaka · JPNational Institute of Biomedical Innovation, Health and Nutrition · JPJapanese Foundation For Cancer Research · JPNHO Kinki Chuo Chest Medical Center · JPOita University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There is an unmet need for novel biomarkers in the diagnosis of multifactorial COPD. We applied next-generation proteomics to serum extracellular vesicles (EVs) to discover novel COPD biomarkers. EVs from 10 patients with COPD and six healthy controls were analysed by tandem mass tag-based non-targeted proteomics, and those from elastase-treated mouse models of emphysema were also analysed by non-targeted proteomics. For validation, EVs from 23 patients with COPD and 20 healthy controls were validated by targeted proteomics. Using non-targeted proteomics, we identified 406 proteins, 34 of which were significantly upregulated in patients with COPD. Of note, the EV protein signature from patients with COPD reflected inflammation and remodelling. We also identified 63 upregulated candidates from 1956 proteins by analysing EVs isolated from mouse models. Combining human and mouse biomarker candidates, we validated 45 proteins by targeted proteomics, selected reaction monitoring. Notably, levels of fibulin-3, tripeptidyl-peptidase 2, fibulin-1, and soluble scavenger receptor cysteine-rich domain-containing protein were significantly higher in patients with COPD. Moreover, six proteins; fibulin-3, tripeptidyl-peptidase 2, UTP-glucose-1-phosphate uridylyl transferase, CD81, CD177, and oncoprotein-induced transcript 3, were correlated with emphysema. Upregulation of fibulin-3 was confirmed by immunoblotting of EVs and immunohistochemistry in lungs. Strikingly,

Identifiers

PMID33778046
PMCPMC7983195
OpenAlexW3137485490

What OpenQuestion holds

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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.