P2X1 and P2X7 Receptor Overexpression Is a Negative Predictor of Survival in Muscle-Invasive Bladder Cancer.
ATP
P2X receptors
P2X1 receptor
P2X7 receptor
T24 cells
biomarker
bladder cancer
muscle-invasive bladder cancer
prognosis
purinergic signaling
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
16 Apr 2023
16 Apr 2023
Historique:
received:
21
03
2023
revised:
10
04
2023
accepted:
14
04
2023
medline:
16
5
2023
pubmed:
16
5
2023
entrez:
16
5
2023
Statut:
epublish
Résumé
Bladder cancer is amongst the most common causes of cancer death worldwide. Muscle-invasive bladder cancer (MIBC) bears a particularly poor prognosis. Overexpression of purinergic P2X receptors (P2XRs) has been associated with worse outcome in several malignant tumors. Here, we investigated the role of P2XRs in bladder cancer cell proliferation in vitro and the prognostic value of P2XR expression in MIBC patients. Cell culture experiments with T24, RT4, and non-transformed TRT-HU-1 cells revealed a link between high ATP concentrations in the cell culture supernatants of bladder cell lines and a higher grade of malignancy. Furthermore, proliferation of highly malignant T24 bladder cancer cells depended on autocrine signaling through P2X receptors. P2X1R, P2X4R, and P2X7R expression was immunohistochemically analyzed in tumor specimens from 173 patients with MIBC. High P2X1R expression was associated with pathological parameters of disease progression and reduced survival time. High combined expression of P2X1R and P2X7R increased the risk of distant metastasis and was an independent negative predictor of overall and tumor-specific survival in multivariate analyses. Our results suggest that P2X1R/P2X7R expression scores are powerful negative prognostic markers in MIBC patients and that P2XR-mediated pathways are potential targets for novel therapeutic strategies in bladder cancer.
Identifiants
pubmed: 37190249
pii: cancers15082321
doi: 10.3390/cancers15082321
pmc: PMC10136747
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NIH HHS
ID : NICHD HD-098363
Pays : United States
Organisme : NIH HHS
ID : NIGMS GM-136429
Pays : United States
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