Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma.
Journal
Translational research : the journal of laboratory and clinical medicine
ISSN: 1878-1810
Titre abrégé: Transl Res
Pays: United States
ID NLM: 101280339
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
01
03
2020
revised:
03
05
2020
accepted:
26
05
2020
pubmed:
4
6
2020
medline:
26
9
2020
entrez:
4
6
2020
Statut:
ppublish
Résumé
Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC. We analyzed human RCC tissue from multiple regions in the primary index tumor, cancer-associated normal adjacent parenchyma, intravascular tumor in locally advanced cancer patients. We found that the higher nuclear Nox4 expression was significantly associated with progression and death. These findings were consistent after controlling for other competing clinical variables. In contrast, patients with lower nuclear Nox4, even in higher stage RCC had better prognosis. We identified a subset of patients with high nuclear Nox4 who had rapid disease progression or died within 6 months of surgery. In addition, higher nuclear Nox4 level correlated with resistance to targeted therapy and immunotherapy. Western blotting performed on fresh human RCC tissue as well as cell-lines revealed increased nuclear Nox4 expression. Our data support an important prognostic role of Nox4 mediated regulation of RCC independent of other competing variables. Nox4 localizes to the nucleus in high-grade, high-stage RCC. Higher nuclear Nox4 has prognostic significance for disease progression, poor survival, and development of drug resistance in RCC.
Identifiants
pubmed: 32492552
pii: S1931-5244(20)30112-2
doi: 10.1016/j.trsl.2020.05.009
pmc: PMC8111697
mid: NIHMS1675209
pii:
doi:
Substances chimiques
NADPH Oxidase 4
EC 1.6.3.-
NOX4 protein, human
EC 1.6.3.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-14Subventions
Organisme : NIGMS NIH HHS
ID : K12 GM111726
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA054174
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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