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

Jiting Sun1,2, Zhiyuan Gong3, Lijie Zheng1,2

  • 1Central Laboratory, Wanbei Coal Electric Group General Hospital, Suzhou, 234011, China.

Scientific Reports
|July 9, 2025
PubMed

Insights

NADPH oxidase 4 (NOX4) drives cancer progression by increasing reactive oxygen species (ROS). Inhibiting NOX4 shows promise for treating multiple cancers, acting as a prognostic biomarker and therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • NADPH oxidase 4 (NOX4) regulates reactive oxygen species (ROS), impacting cancer development and progression.
  • NOX4 influences cancer cell transformation, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).

Purpose of the Study:

  • To investigate the role of NOX4 in tumorigenesis across multiple cancer types using pan-cancer analysis.
  • To correlate NOX4 expression with patient prognosis, immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI).
  • To validate NOX4's function in breast cancer cell proliferation and metastasis through in vitro experiments.

Main Methods:

  • Comprehensive pan-cancer bioinformatics analysis using The Cancer Genome Atlas (TCGA) data.
  • Systematic analysis of NOX4 expression patterns and correlations with clinical/molecular features.
  • In vitro validation using wound healing, Transwell, and CCK-8 assays in breast cancer cells.

Main Results:

  • NOX4 is significantly upregulated in various cancers, including breast cancer.
  • Elevated NOX4 expression correlates with poorer patient prognosis, increased immune cell infiltration, higher TMB, and MSI.
  • Downregulating NOX4 inhibited proliferation and metastasis in breast cancer cells.

Conclusions:

  • NOX4 plays a significant role in pan-cancer tumorigenesis.
  • NOX4 is a potential prognostic biomarker and therapeutic target for various cancers.
  • Targeting NOX4 may offer a novel strategy for anti-tumor treatments.

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