Evidence map›Paper›PMID 41516353›Full record

ArticleInternational journal of molecular sciences2026

Identification of a Muscle-Invasive Bladder Carcinoma Molecular Subtype of Poor Responders to Neoadjuvant Chemotherapy and High Expression of Targetable Biomarkers.

Lucía Trilla-Fuertes, Jorge Pedregosa-Barbas, Eugenia García-Fernández, Francisco Zambrana, Imanol Martínez-Salas, Pablo Gajate, Fernando Becerril-Gómez, Pedro Lalanda-Delgado, Antje Dittmann, Rocío López-Vacas and 8 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2026. 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. Review
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

18 authors.

Lucía Trilla-FuertesMolecular Oncology Lab, INGEMM, La Paz University Hospital-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.ORCID 0000-0002-4452-3474
Jorge Pedregosa-BarbasMedical Oncology Service, La Paz University Hospital-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.
Eugenia García-FernándezDepartment of Pathology, La Paz University Hospital-IdiPAZ, UAM, 28046 Madrid, Spain.ORCID 0000-0002-3850-1906
Francisco ZambranaMedical Oncology Department, Infanta Sofía University Hospital, 28702 Madrid, Spain.ORCID 0000-0003-2815-7731
Imanol Martínez-SalasMedical Oncology Department, IIS-FJD, University Hospital Fundación Jiménez Díaz, 28040 Madrid, Spain.
Pablo GajateMedical Oncology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.ORCID 0000-0001-5156-7080
Fernando Becerril-GómezMolecular Oncology Lab, INGEMM, La Paz University Hospital-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.ORCID 0009-0007-3726-050X
Pedro Lalanda-DelgadoMolecular Oncology Lab, INGEMM, La Paz University Hospital-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.
Antje DittmannFunctional Genomics Center Zurich, University of Zurich/ETH Zurich, 8057 Zurich, Switzerland.ORCID 0000-0002-2570-5192
Rocío López-VacasMolecular Oncology Lab, INGEMM, La Paz University Hospital-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.
Laura KunzFunctional Genomics Center Zurich, University of Zurich/ETH Zurich, 8057 Zurich, Switzerland.
Gustavo RubioMedical Oncology Department, Infanta Sofía University Hospital, 28702 Madrid, Spain.
Sandra Nieto-TorreroIdiPAZ Biobank, La Paz University Hospital-IdiPAZ, 28046 Madrid, Spain.
Ana PertejoMedical Oncology Service, La Paz University Hospital-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.
Pilar González-PeramatoDepartment of Pathology, La Paz University Hospital-IdiPAZ, UAM, 28046 Madrid, Spain.
Juan Ángel Fresno VaraMolecular Oncology Lab, INGEMM, La Paz University Hospital-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.ORCID 0000-0003-1527-1252
Angelo Gámez-PozoMolecular Oncology Lab, INGEMM, La Paz University Hospital-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.ORCID 0000-0002-8931-0624
Álvaro Pinto-MarínMedical Oncology Service, La Paz University Hospital-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.ORCID 0000-0002-4719-053X

Funding

European Proteomics Infrastructure Consortium 823839
6 · The paper itself

Abstract

Neoadjuvant chemotherapy (NACT) is the standard treatment for muscle-invasive bladder carcinoma (MIBC), but its efficacy varies significantly among patients. The aim of this study is the identification of biomarkers and biological processes related to the response to neoadjuvant chemotherapy (NACT) in muscle-invasive bladder carcinoma (MIBC). Fifty-eight transurethral resection (TURBT) samples and thirty cystectomy samples from NACT non-responders were analyzed using mass spectrometry. Samples were classified with sparse k-means and consensus clustering. Protein networks were built using probabilistic graphical models, grouped into functional nodes, and analyzed for activity differences. Gene set enrichment analysis was applied to identify resistance mechanisms, and results were validated using The Cancer Genome Atlas (TCGA) cohort. Proteomic analysis revealed two independent classifications in TURBT samples. The first (Layer1) divided tumors into three groups, including one NACT non-responder subtype not aligned with traditional luminal or basal classifications but characterized by high expression of targetable markers NECTIN4 and Her2. The second (Layer3) separated luminal-papillary tumors from luminal-infiltrated/luminal and basal tumors. While Layer3 groups did not differ in NACT response, they showed distinct disease-free survival outcomes. Importantly, complete response to NACT was linked to improved survival in luminal subgroups but not in basal tumors, suggesting subtype-specific prognostic implications. Finally, analysis of cystectomy samples identified unique mechanisms of resistance for each subgroup, suggesting tailored therapeutic approaches. Two classification systems were defined as follows: one identified a proteomics-based non-responder group with actionable targets, and the other linked tumor subtype to prognosis. Distinct resistance mechanisms suggest opportunities for subtype-specific therapies, supporting improved management and treatment development for MIBC patients.

Indexed as

Biomarkers, TumorNeoadjuvant TherapyUrinary Bladder NeoplasmsAgedFemaleHumansMaleNeoplasm InvasivenessPrognosisProteomicsTransurethral Resection of BladderBiomarkers, Tumormuscle-invasive bladder cancerproteomics subtyperesponse to neoadjuvant chemotherapytargetable biomarkers

Identifiers

PMID41516353
PMCPMC12787041

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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.