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pmid:31991796

Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer.

Giulio Eugenio Mandelli · Francesco Missale · Debora Bresciani · Luisa Benerini Gatta · Patrizia Scapini · Elena Caveggion · Elisa Roca · Mattia Bugatti · Matilde Monti · Luca Cristinelli · Sandra Belotti · Claudio Simeone · Stefano Calza · Laura Melocchi · William Vermi

Cells · 2020 doi:10.3390/cells9020291

Paper

complete

Experiment

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Data

partial

Analysis

partial

Execution

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title
Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer.
doi
10.3390/cells9020291
pmid
31991796
authors array · 15 items
[0]
Giulio Eugenio Mandelli
[1]
Francesco Missale
[2]
Debora Bresciani
[3]
Luisa Benerini Gatta
[4]
Patrizia Scapini
[5]
Elena Caveggion
[6]
Elisa Roca
[7]
Mattia Bugatti
[8]
Matilde Monti
[9]
Luca Cristinelli
[10]
Sandra Belotti
[11]
Claudio Simeone
[12]
Stefano Calza
[13]
Laura Melocchi
[14]
William Vermi
journal
Cells
year
2020
abstract
BACKGROUND: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy. METHODS: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b+ tumor-associated-neutrophils (TAN) and CD3+ T cells. Bioinformatics analysis of UBC datasets and gene expression analysis of UBC cell lines were additionally performed. RESULTS: Basal type BC contained a significantly higher density of CD66b+ TAN compared to the luminal type. This finding was validated on TCGA, GSE32894 and GSE124305 datasets by computing a neutrophil signature. Of note, basal-type MIBC display a significantly higher level of chemokines (CKs) attracting neutrophils. Moreover, pro-inflammatory stimuli significantly up-regulate CXCL1, CXCL2 and CXCL8 in 5637 and RT4 UBC cell lines and induce neutrophil chemotaxis. In term of survival, a high density of T celsl and TAN was significantly associated to a better outcome, with TAN density showing a more limited statistical power and following a non-linear predicting model. CONCLUSIONS: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.
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Univariate and multivariate survival analyses were performed using Cox proportional hazard models; multivariable models were built by a backward selection applying Likelihood-ratio test and Akaike information criterion; estimates were reported as hazard ratio (HR) with 95% Confidence Intervals (CI95%).
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Univariate and multivariate survival analyses were performed using Cox proportional hazard models; multivariable models were built by a backward selection applying Likelihood-ratio test and Akaike information criterion; estimates were reported as hazard ratio (HR) with 95% Confidence Intervals (CI95%).
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Formalin fixed paraffin-embedded (FFPE) UBC were retrieved from the archive of the Department of Pathology, ASST Spedali Civili di Brescia (Brescia, Italy). Clinical follow-up data were retrieved from the Department of Urology, ASST Spedali Civili di Brescia (Brescia, Italy).
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Formalin fixed paraffin-embedded (FFPE) UBC were retrieved from the archive of the Department of Pathology, ASST Spedali Civili di Brescia (Brescia, Italy). Clinical follow-up data were retrieved from the Department of Urology, ASST Spedali Civili di Brescia (Brescia, Italy).
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Formalin fixed paraffin-embedded (FFPE) UBC were retrieved from the archive of the Department of Pathology, ASST Spedali Civili di Brescia (Brescia, Italy). Clinical follow-up data were retrieved from the Department of Urology, ASST Spedali Civili di Brescia (Brescia, Italy).
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null
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6947
taxon
Homo sapiens
title
A Molecular Taxonomy of Urothelial Carcinoma
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2026-11-01T15:39:54Z
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Univariate and multivariate survival analyses were performed using Cox proportional hazard models; multivariable models were built by a backward selection applying Likelihood-ratio test and Akaike information criterion; estimates were reported as hazard ratio (HR) with 95% Confidence Intervals (CI95%).
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The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: mann_whitney.
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owned
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Formalin fixed paraffin-embedded (FFPE) UBC were retrieved from the archive of the Department of Pathology, ASST Spedali Civili di Brescia (Brescia, Italy). Clinical follow-up data were retrieved from the Department of Urology, ASST Spedali Civili di Brescia (Brescia, Italy).
basis
The paper names GSE32894, GSE124305 in GSE32894 dataset and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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minimax
read_at
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independence
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31991796", "kind": "science-record", "revision": 8, "content_hash": "sha256:490450990f12d859e53ba15d84a7383a04dae7a821d6cdd74f8400fe824fd3de", "created_at": "2026-11-01T15:40:55Z", "updated_at": "2026-11-01T22:01:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer.", "doi": "10.3390/cells9020291", "pmid": "31991796", "authors": ["Giulio Eugenio Mandelli", "Francesco Missale", "Debora Bresciani", "Luisa Benerini Gatta", "Patrizia Scapini", "Elena Caveggion", "Elisa Roca", "Mattia Bugatti", "Matilde Monti", "Luca Cristinelli", "Sandra Belotti", "Claudio Simeone", "Stefano Calza", "Laura Melocchi", "William Vermi"], "journal": "Cells", "year": 2020, "abstract": "BACKGROUND: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy.\nMETHODS: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b+ tumor-associated-neutrophils (TAN) and CD3+ T cells. Bioinformatics analysis of UBC datasets and gene expression analysis of UBC cell lines were additionally performed.\nRESULTS: Basal type BC contained a significantly higher density of CD66b+ TAN compared to the luminal type. This finding was validated on TCGA, GSE32894 and GSE124305 datasets by computing a neutrophil signature. Of note, basal-type MIBC display a significantly higher level of chemokines (CKs) attracting neutrophils. Moreover, pro-inflammatory stimuli significantly up-regulate CXCL1, CXCL2 and CXCL8 in 5637 and RT4 UBC cell lines and induce neutrophil chemotaxis. In term of survival, a high density of T celsl and TAN was significantly associated to a better outcome, with TAN density showing a more limited statistical power and following a non-linear predicting model.\nCONCLUSIONS: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate survival analyses were performed using Cox proportional hazard models; multivariable models were built by a backward selection applying Likelihood-ratio test and Akaike information criterion; estimates were reported as hazard ratio (HR) with 95% Confidence Intervals (CI95%).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31991796", "locator": "sections[6] \"2.4. 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Patient’s Cohort\" paragraph 2", "quote": "Formalin fixed paraffin-embedded (FFPE) UBC were retrieved from the archive of the Department of Pathology, ASST Spedali Civili di Brescia (Brescia, Italy). Clinical follow-up data were retrieved from the Department of Urology, ASST Spedali Civili di Brescia (Brescia, Italy)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31991796"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE124305"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_mann_whitney", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE124305"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31991796", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/cells9020291", "sha256": "sha256:499abf5373af2ea42eba46f48315ef11b35fd8e19f1c452ad2d7d5e11d444d6b", "bytes": 41997, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/cells9020291", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7072276", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE124305", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE124305", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE124305", "version": null, "note": "Formalin fixed paraffin-embedded (FFPE) UBC were retrieved from the archive of the Department of Pathology, ASST Spedali Civili di Brescia (Brescia, Italy). 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