ArticleTranslational research : the journal of laboratory and clinical medicine2020
Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma.
Article in Translational research : the journal of laboratory and clinical medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- NOX4 as an emerging prognostic and immunological biomarker across pan-cancer analyses.Scientific reports · 2025Article
- The Lipid-Oxidative Stress Axis: Novel Therapeutic Targets for Podocytopathy.Journal of inflammation research · 2025Review
- Targeting ROS production through inhibition of NADPH oxidases.Nature chemical biology · 2023Article
- NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores.Cellular and molecular life sciences : CMLS · 2023Article
- NADPH Oxidase 4: A Potential Therapeutic Target of Malignancy.Frontiers in cell and developmental biology · 2022Review
- Article
- NOX4: a potential therapeutic target for pancreatic cancer and its mechanism.Journal of translational medicine · 2021Review
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
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.
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