NOX4 serves as a pan-cancer prognostic biomarker and therapeutic target in tumorigenesis

Abstract NADPH oxidase 4 (NOX4) is a key regulator of intracellular reactive oxygen species (ROS) and plays a critical role in tumorigenesis and cancer progression. It contributes to cancer cell transformation, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). To eluci...

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Main Authors: Jiting Sun, Zhiyuan Gong, Lijie Zheng, Zhixian Ding, Lusheng Wang, Yu Tang, Shizhan Deng, Yonggan Dong, Heng Tang
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-09690-9
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Summary:Abstract NADPH oxidase 4 (NOX4) is a key regulator of intracellular reactive oxygen species (ROS) and plays a critical role in tumorigenesis and cancer progression. It contributes to cancer cell transformation, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). To elucidate the molecular mechanisms underlying NOX4-mediated tumorigenesis, we performed a comprehensive pan-cancer bioinformatics analysis, integrating data from The Cancer Genome Atlas (TCGA), and validated our findings with in vitro experiments. We systematically analyzed NOX4 expression patterns across various cancer types and explored the correlations between NOX4 expression and patient survival, immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). In vitro assays, including Wound healing, Transwell, and CCK-8 assays, were conducted to validate the biological functions of NOX4 in breast cancer cells. Pan-cancer analysis revealed that NOX4 is significantly upregulated in various cancers, including breast cancer. Elevated NOX4 expression is associated with poor patient prognosis, immune cell infiltration, TMB, and MSI. Functional experiments confirmed that downregulation of NOX4 can inhibit the proliferation and metastasis of breast cancer cells. Our pan-cancer analysis provides valuable insights into the role of NOX4 in tumorigenesis. These results highlight NOX4 as a promising biomarker for prognosis and a potential therapeutic target for anti-tumor treatments across multiple cancer types.
ISSN:2045-2322