Evidence map›Paper›PMID 33721374›Full record

ArticleCancer science2021

Proteomic analysis of urinary and tissue-exudative extracellular vesicles to discover novel bladder cancer biomarkers.

Eisuke Tomiyama, Kyosuke Matsuzaki, Kazutoshi Fujita, Takashi Shiromizu, Ryohei Narumi, Kentaro Jingushi, Yoko Koh, Makoto Matsushita, Kosuke Nakano, Yujiro Hayashi and 11 more

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

48 citing papers in PubMed, 68 citations in OpenAlex.

  1. Urinary Extracellular Vesicle-Associated EphA2 Predicts Intravesical Recurrence in Bladder Cancer.International journal of urology : official journal of the Japanese Urological Association · 2026
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  15. Protein dysregulation duringFrontiers in immunology · 2025
    Article
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  17. Prospects and challenges of tissue-derived extracellular vesicles.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
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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

21 authors at 5 institutions in 1 country.

Eisuke TomiyamaDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.ORCID https://orcid.org/0000-0002-0056-9446
Kyosuke MatsuzakiDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.ORCID https://orcid.org/0000-0002-7137-1162
Kazutoshi FujitaDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Takashi ShiromizuLaboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Ryohei NarumiLaboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Kentaro JingushiLaboratory of Molecular and Cellular Physiology, Osaka University Graduate School of Pharmaceutical Sciences, Suita, Japan.
Yoko KohDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Makoto MatsushitaDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Kosuke NakanoDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.ORCID https://orcid.org/0000-0001-5356-7359
Yujiro HayashiDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.ORCID https://orcid.org/0000-0002-4701-5635
Cong WangDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.ORCID https://orcid.org/0000-0001-8445-6205
Yu IshizuyaDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Taigo KatoDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.ORCID https://orcid.org/0000-0002-8681-1407
Koji HatanoDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Atsunari KawashimaDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.ORCID https://orcid.org/0000-0001-9369-4264
Takeshi UjikeDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Motohide UemuraDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Tetsuya TakaoDepartment of Urology, Osaka General Medical Center, Osaka, Japan.
Jun AdachiLaboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.ORCID https://orcid.org/0000-0003-1220-3246
Takeshi TomonagaLaboratory of Proteome Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.
Norio NonomuraDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Japan.ORCID https://orcid.org/0000-0002-6522-6233
The University of Osaka · JPNational Institute of Biomedical Innovation, Health and Nutrition · JPOsaka Gakuin University · JPKindai University · JPOsaka Prefectural Medical Center · JP

Funding

Japan Agency for Medical Research and Development A102Japan Society for the Promotion of Science JP17K16788
6 · The paper itself

Abstract

Proteomic analysis of urinary extracellular vesicles (EVs) is a powerful approach to discover potential bladder cancer (BCa) biomarkers, however urine contains numerous EVs derived from the kidney and normal urothelial epithelium, which can obfuscate information related to BCa cell-derived EVs. In this study, we combined proteomic analysis of urinary EVs and tissue-exudative EVs (Te-EVs), which were isolated from culture medium of freshly resected viable BCa tissues. Urinary EVs were isolated from urine samples of 11 individuals (7 BCa patients and 4 healthy individuals), and Te-EVs were isolated from 7 BCa tissues. We performed tandem mass tag (TMT)-labeling liquid chromatography (LC-MS/MS) analysis for both urinary EVs and Te-EVs and identified 1960 proteins in urinary EVs and 1538 proteins in Te-EVs. Most of the proteins identified in Te-EVs were also present in urinary EVs (82.4%), with 55 of these proteins showing upregulated levels in the urine of BCa patients (fold change > 2.0; P < .1). Among them, we selected 22 membrane proteins as BCa biomarker candidates for validation using selected reaction monitoring/multiple reaction monitoring (SRM/MRM) analysis on urine samples from 70 individuals (40 BCa patients and 30 healthy individuals). Six urinary EV proteins (heat-shock protein 90, syndecan-1, myristoylated alanine-rich C-kinase substrate (MARCKS), MARCKS-related protein, tight junction protein ZO-2, and complement decay-accelerating factor) were quantified using SRM/MRM analysis and validated as significantly upregulated in BCa patients (P < .05). In conclusion, the novel strategy that combined proteomic analysis of urinary EVs and Te-EVs enabled selective detection of urinary BCa biomarkers.

Indexed as

Exudates and TransudatesAdultAgedBiomarkers, TumorCase-Control StudiesChromatography, LiquidExtracellular VesiclesFemaleHumansMaleMiddle AgedNeoplasm ProteinsProteomicsUp-RegulationUrinary Bladder NeoplasmsBiomarkers, TumorNeoplasm Proteinsbladder cancerexosomeextracellular vesicleproteomicsurinary biomarker

Identifiers

PMID33721374
PMCPMC8088963
OpenAlexW3136578782

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.