Evidence map›Paper›PMID 31326313›Full record

ArticleUrologic oncology2019

Predictive value of phenotypic signatures of bladder cancer response to cisplatin-based neoadjuvant chemotherapy.

Patrick J Hensley, Natasha Kyprianou, Matthew S Purdom, Daheng He, Vincent DiCarlo, Chi Wang, Andrew C James

Open access · greenAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Urologic oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 17% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
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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

7 authors at 1 institution in 1 country.

Patrick J HensleyDepartment of Urology, University of Kentucky College of Medicine, Lexington, KY; Department of Pathology, University of Kentucky College of Medicine, Lexington, KY. Electronic address: patrick.hensley@uky.edu.
Natasha KyprianouDepartment of Urology, University of Kentucky College of Medicine, Lexington, KY; Department of Pathology, University of Kentucky College of Medicine, Lexington, KY; Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY.
Matthew S PurdomDepartment of Pathology, University of Kentucky College of Medicine, Lexington, KY.
Daheng HeDepartment of Cancer Biostatistics, University of Kentucky College of Medicine, Lexington, KY.
Vincent DiCarloDepartment of Urology, University of Kentucky College of Medicine, Lexington, KY.
Chi WangDepartment of Cancer Biostatistics, University of Kentucky College of Medicine, Lexington, KY.
Andrew C JamesDepartment of Urology, University of Kentucky College of Medicine, Lexington, KY.
University of Kentucky · US

Funding

University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI KATHLEEN L. O'CONNOR · 2013 to 2026
$38.3M
NCI NIH HHS P30 CA177558
6 · The paper itself

Abstract

backgroundCisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive urothelial carcinoma of the bladder confers only a modest survival advantage. Patients with pathologic progression on NAC have poor outcomes related to a delay in definitive surgical management.

objectiveTo characterize the value of epithelial-mesenchymal transition (EMT) effectors and other novel biomarkers to predict response to NAC.

methodsA tissue microarray was constructed from patients with clinical stage T2 urothelial carcinoma of the bladder using transurethral resection (TUR) specimens (N = 69) and case-matched post-NAC cystectomy specimens (N = 51). Patients were stratified based on pathologic response to NAC and cancer-specific survival. Biomarker expression in TUR specimens was correlated with pathologic response to NAC and clinical outcomes. Phenotypic changes in expression induced by cisplatin-based NAC were characterized in primary TUR and post-NAC cystectomy and lymph node metastasis specimens.

resultsIncreased expression of mesenchymal markers and actin-cytoskeleton regulators, as well as low apoptosis index, in TUR specimens was associated with pathologic progression on cisplatin-based NAC. Overexpression of N-cadherin and decreased apoptosis was predictive of disease-specific mortality. NAC decreased cofilin phosphorylation and induced a mesenchymal-epithelial transition phenotype.

conclusionsThe epithelial-mesenchymal transition phenotype and actin-cytoskeleton remodeling are associated with pathologic progression on NAC. Chemotherapy induced an mesenchymal-epithelial transition phenotype and decreased cofilin phosphorylation, providing new insights into therapeutic resistance mechanisms. Primary tumors with high apoptosis rates exhibited favorable response to NAC and lower mortality rates, indicating that these tumors may be sensitized to therapy. Further validation will establish these novel signatures as predictors of therapeutic response.

Indexed as

AgedChemotherapy, AdjuvantCisplatinEpithelial-Mesenchymal TransitionFemaleHumansImmunohistochemistryMaleMiddle AgedPhenotypeProspective StudiesTreatment OutcomeUrinary Bladder NeoplasmsCisplatinBiomarkerCisplatinEpithelial-mesenchymal transitionNeoadjuvant chemotherapyPathologic responseUrothelial carcinoma

Identifiers

PMID31326313
PMCPMC9186422
OpenAlexW2960990283

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.