Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma
Ashcraft, Keith A
Shah, Pankil K
Tye, Cooper B
Liss, Michael A
Pruthi, Deepak K
Mansour, Ahmed M
Watson, Amanda L
AffiliationUniv Arizona, Dept Cellular & Mol Med
MetadataShow full item record
PublisherELSEVIER SCIENCE INC
CitationKaushik, D., Ashcraft, K. A., Wang, H., Shanmugasundaram, K., Shah, P., Gonzalez, G., ... & Mansour, A. M. (2020). Nuclear NADPH Oxidase-4 Associated With Disease Progression In Renal Cell Carcinoma. Translational Research.
RightsCopyright © 2020 Elsevier Inc. All rights reserved.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractNuclear 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.
Note12 month embargo; published 31 May 2020
VersionFinal accepted manuscript
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