Transcriptomic and Protein Analysis of Small-cell Bladder Cancer (SCBC) Identifies Prognostic Biomarkers and DLL3 as a Relevant Therapeutic Target.
Adult
Aged, 80 and over
Animals
Biomarkers, Tumor
/ genetics
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Heterografts
Humans
Immunoconjugates
/ immunology
Intracellular Signaling Peptides and Proteins
/ genetics
Male
Membrane Proteins
/ genetics
Mice
Middle Aged
Prognosis
Proteome
/ genetics
Transcriptome
/ genetics
Urinary Bladder Neoplasms
/ drug therapy
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 01 2019
01 01 2019
Historique:
received:
26
04
2018
revised:
07
09
2018
accepted:
08
10
2018
pubmed:
18
10
2018
medline:
27
2
2020
entrez:
18
10
2018
Statut:
ppublish
Résumé
Transcriptomic profiling can shed light on the biology of small-cell bladder cancer (SCBC), nominating biomarkers, and novel therapeutic targets. Sixty-three patients with SCBC had small-cell histology confirmed and quantified by a genitourinary pathologist. Gene expression profiling was performed for 39 primary tumor samples, 1 metastatic sample, and 6 adjacent normal urothelium samples (46 total) from the same cohort. Protein levels of differentially expressed therapeutic targets, DLL3 and PDL1, and also CD56 and ASCL1, were confirmed by IHC. A SCBC PDX model was utilized to assess Unsupervised hierarchical clustering of 46 samples produced 4 clusters that correlated with clinical phenotypes. Patients whose tumors had the most "normal-like" pattern of gene expression had longer overall survival (OS) compared with the other 3 clusters while patients with the most "metastasis-like" pattern had the shortest OS ( Gene expression patterns in SCBC are associated with distinct clinical phenotypes ranging from more indolent to aggressive disease. Overexpression of
Identifiants
pubmed: 30327311
pii: 1078-0432.CCR-18-1278
doi: 10.1158/1078-0432.CCR-18-1278
pmc: PMC6333466
mid: NIHMS1509723
doi:
Substances chimiques
Biomarkers, Tumor
0
DLL3 protein, human
0
Immunoconjugates
0
Intracellular Signaling Peptides and Proteins
0
Membrane Proteins
0
Proteome
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
210-221Subventions
Organisme : NCI NIH HHS
ID : L30 CA220908
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA043703
Pays : United States
Informations de copyright
©2018 American Association for Cancer Research.
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