Sun Jiting, Gong Zhiyuan, Zheng Lijie, Ding Zhixian, Wang Lusheng, Tang Yu, Deng Shizhan, Dong Yonggan, Tang Heng
Central Laboratory, Wanbei Coal Electric Group General Hospital, Suzhou, 234011, China.
Laboratory of Inflammation and Repair of Liver Injury and Tumor Immunity, Hefei, 230000, China.
Sci Rep. 2025 Jul 9;15(1):24612. doi: 10.1038/s41598-025-09690-9.
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.
NADPH氧化酶4（NOX4）是细胞内活性氧（ROS）的关键调节因子，在肿瘤发生和癌症进展中起关键作用。它有助于癌细胞的转化、增殖、迁移、侵袭和上皮-间质转化（EMT）。为了阐明NOX4介导肿瘤发生的分子机制，我们进行了全面的泛癌生物信息学分析，整合了来自癌症基因组图谱（TCGA）的数据，并用体外实验验证了我们的发现。我们系统地分析了NOX4在各种癌症类型中的表达模式，并探讨了NOX4表达与患者生存率、免疫浸润、肿瘤突变负担（TMB）和微卫星不稳定性（MSI）之间的相关性。进行了包括伤口愈合、Transwell和CCK-8实验在内的体外实验，以验证NOX4在乳腺癌细胞中的生物学功能。泛癌分析显示，NOX4在包括乳腺癌在内的各种癌症中显著上调。NOX4表达升高与患者预后不良、免疫细胞浸润、TMB和MSI相关。功能实验证实，NOX4的下调可抑制乳腺癌细胞的增殖和转移。我们的泛癌分析为NOX4在肿瘤发生中的作用提供了有价值的见解。这些结果突出了NOX4作为一种有前景的预后生物标志物以及多种癌症类型抗肿瘤治疗的潜在靶点。
