Evidence map›Paper›PMID 40365898›Full record

ArticleCancer medicine2025

EIF2S1 in Urinary Extracellular Vesicles as a Novel Diagnostic Marker for Bladder Cancer.

Eisuke Tomiyama, Kazutoshi Fujita, Kyosuke Matsuzaki, Ryohei Narumi, Makoto Matsushita, Yujiro Hayashi, Mamoru Hashimoto, Taigo Kato, Koji Hatano, Atsunari Kawashima and 7 more

Abstract readValidation Study
In one paragraph

Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

17 authors.

Eisuke TomiyamaDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.ORCID https://orcid.org/0000-0002-0056-9446
Kazutoshi FujitaDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kyosuke MatsuzakiDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Ryohei NarumiLaboratory of Proteomics for Drug Discovery, Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Makoto MatsushitaDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yujiro HayashiDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Mamoru HashimotoDepartment of Urology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
Taigo KatoDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Koji HatanoDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.ORCID https://orcid.org/0000-0002-8409-5152
Atsunari KawashimaDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takafumi MinamiDepartment of Urology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
Tetsuya TakaoDepartment of Urology, Osaka General Medical Center, Osaka, Osaka, Japan.
Shingo TakadaDepartment of Urology, Osaka Police Hospital, Osaka, Osaka, Japan.
Hirotsugu UemuraDepartment of Urology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.ORCID https://orcid.org/0000-0002-3665-9523
Jun AdachiLaboratory of Proteomics for Drug Discovery, Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.ORCID https://orcid.org/0000-0003-1220-3246
Takeshi TomonagaLaboratory of Proteomics for Drug Discovery, Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Norio NonomuraDepartment of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.ORCID https://orcid.org/0000-0002-6522-6233

Funding

Japan Agency for Medical Research and Development A102Japan Society for the Promotion of Science 17K16788Japan Society for the Promotion of Science 20K18140
6 · The paper itself

Abstract

backgroundUrinary extracellular vesicles (uEVs), directly secreted from bladder cancer (BCa) cells, harbor potential for biomarker discovery.

methodsWe performed proteomic analysis to explore and validate uEV-based diagnostic markers for BCa, with a focus on cytoplasmic EV proteins. Among the 1960 proteins identified by shotgun proteomics (tandem mass tag-labeled liquid chromatography-tandem mass spectrometry [LC-MS/MS]) of uEVs from seven patients with BCa and four healthy individuals, 17 cytoplasmic EV proteins were significantly elevated in the patients' urine (fold change > 1.5; p < 0.05). These 17 proteins were subsequently validated using targeted proteomics (selected reaction monitoring/multiple reaction monitoring) using urine samples from 49 and 48 patients with and without BCa, respectively, including those with non-BCa hematuria.

resultsTen measurable EV proteins remained significantly elevated in the urine of patients with BCa, with EV-EIF2S1 demonstrating the best diagnostic performance (area under the receiver operating characteristic [ROC] curve [AUC] [ROCAUC]: 0.83). Additionally, EV-EIF2S1 distinguished patients with BCa from those without BCa and hematuria in a suitable manner (ROCAUC: 0.92). Functional analysis of EIF2S1 in the BCa cell lines (T24 and 5637) showed that EIF2S1 knockdown markedly inhibited cell proliferation and induced cell cycle arrest and apoptosis, suggesting its essentiality for BCa cell growth and survival.

conclusionsThis study identified EV-EIF2S1 as a novel, uEV-based BCa diagnostic marker and demonstrated its functional significance in BCa cell growth and survival.

Indexed as

Biomarkers, TumorClinical RelevanceEukaryotic Initiation Factor-2Urinary Bladder NeoplasmsAdultAgedApoptosisArea Under CurveCase-Control StudiesCell Line, TumorCell ProliferationExtracellular VesiclesFemaleHumansLiquid Chromatography-Mass SpectrometryMaleBiomarkers, TumorEIF2S1 protein, humanEukaryotic Initiation Factor-2bladder cancercytoplasmic proteinsextracellular vesiclesliquid biopsyproteomicsurinary markers

Identifiers

PMID40365898
PMCPMC12076193

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.