Evidence map›Paper›PMID 41981705›Full record

ArticleBiomarker research2026

Soluble immune checkpoints as diagnostic biomarkers in bladder cancer.

Anna Andrzejczak, Wojciech Krajewski, Emilia Jaskuła, Joanna Chorbińska, Anna Tomkiewicz, Krystian Sarat, Robert Mroczek, Bartosz Małkiewicz, Tomasz Szydełko, Lidia Karabon

Abstract readLetter
In one paragraph

Article in Biomarker research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Anna AndrzejczakLaboratory of Genetic and Epigenetic of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Wojciech KrajewskiUniversity Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, Wrocław, Poland.
Emilia JaskułaLaboratory of Genetic and Epigenetic of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Joanna ChorbińskaUniversity Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, Wrocław, Poland.
Anna TomkiewiczLaboratory of Genetic and Epigenetic of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Krystian SaratLaboratory of Genetic and Epigenetic of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Robert MroczekLaboratory of Genetic and Epigenetic of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Bartosz MałkiewiczUniversity Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, Wrocław, Poland.
Tomasz SzydełkoUniversity Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, Wrocław, Poland.
Lidia KarabonLaboratory of Genetic and Epigenetic of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. lidia.karabon@hirszfeld.pl.

Funding

Research grants from Wroclaw Medical University Institutional Review Board Statement SUBZ.C090.095
6 · The paper itself

Abstract

Bladder cancer (BC) is a common malignancy with high recurrence and substantial monitoring costs. Limitations of current diagnostic tools: cystoscopy is invasive and expensive, urine cytology lacks sensitivity and existing urine biomarkers cannot replace cystoscopy, underscoring the need for improved non-invasive methods. Immune checkpoints (ICs) regulate immune activity, and newer ICs: T-cell immunoglobulin and mucin domain 3 (TIM-3), galectin-9 (Gal-9), B- and T-lymphocyte attenuator (BTLA), herpesvirus entry mediator (HVEM), cluster of differentiation 160 (CD160), and lymphocyte-activation gene 3 (LAG-3), are involved in cancer immune evasion. This study demonstrated that levels of soluble ICs (sICs) are markedly elevated in patients with early-stage BC. Serum levels of sTIM-3, sGal-9, sBTLA, sHVEM, sCD160, and sLAG-3 were quantified in BC and controls. sTIM-3, sGal-9, and sBTLA were significantly elevated in BC, while their concentrations didn’t vary by tumor stage or grade, supporting diagnostic rather than prognostic utility. Whereas sHVEM, sCD160, and sLAG-3 showed no diagnostic value. Age, sex, and body mass index (BMI) had minimal influence on sIC levels. Receiver operating characteristic (ROC) analyses showed strong performance: sGal-9 was the best classifier (area under the curve (AUC) = 0.98; 91% sensitivity; 100% specificity), followed by sTIM-3 (AUC = 0.91) and sBTLA (AUC = 0.78). sHVEM, sCD160, sLAG-3 performed poorly. A multivariate model incorporating sGal-9, sTIM-3, and sBTLA achieved a cross-validated AUC = 0.982, with sGal-9 remaining independently predictive. Correlation analyses revealed two clusters: sGal-9/sTIM-3/sBTLA and sHVEM/sCD160, that relationships align with known receptor-ligand biology and may reflect shedding during T-cell exhaustion. Overall, sGal-9, supported by sTIM-3 and sBTLA, constitutes promising serum biomarker panel associated with early-stage BC, however, as these markers are not disease-specific and may be affected by inflammatory or other pathological conditions, further validation is required.

Indexed as

Bladder cancerDisease riskImmune checkpointsSoluble isoforms

Identifiers

PMID41981705
PMCPMC13081242

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.