Ferroptosis-Related genes NOX4, PDK4, PRKAA2, and FABP4 Emerge as Novel Prognostic Biomarkers and Therapeutic Targets in Stomach Adenocarcinoma

ORIGINAL ARTICLE
Qinmin Liu, Fei Wang, Yongjin Luo, Qi Guo, Yichi Zhang, Fanghui Chen, Shaoqiang Liu

 
For citation: Liu Q, Wang F, Luo Y, Guo Q, Zhang Y, Chen F, Liu S. Ferroptosis-Related genes NOX4, PDK4, PRKAA2, and FABP4 Emerge as Novel Prognostic Biomarkers and Therapeutic Targets in Stomach Adenocarcinoma. International Journal of Biomedicine. 2025;15(3):483-489. doi:10.21103/Article15(3)_OA3
 
Originally published September 5, 2025

Abstract: 

Background: Stomach adenocarcinoma (STAD) is the fifth most common malignant tumor worldwide in terms of both incidence and mortality. Treatment and prognosis face great challenges. We aimed to identify potential therapeutic targets or prognostic genes by analyzing STAD RNA-seq and clinical data, as well as ferroptosis-related genes.
Methods and Results: RNA-seq and clinical data of STAD were downloaded from the Cancer Genome Atlas (TCGA) database, and ferroptosis-related gene data were downloaded from the FerrDb V2 website. Bioinformatics and statistical analyses were performed using R software, and statistical significance was set at P<0.05.
We screened 1384 differentially expressed genes (DEGs) between STAD and normal tissues, including 24 ferroptosis-related DEGs. Among these 24 genes, we further screened four hub genes related to survival prognosis: NOX2, PRKAA2, FABP4, and PDK4. Through single-gene survival analysis and Cox regression analysis, and by constructing a prognostic model, we found that STAD patients with low expression of NOX2, PRKAA2, FABP4, and PDK4 had significantly longer survival times; the difference was statistically significant (P<0.05).
Conclusion: We identified four ferroptosis-related DEGs in STAD that are associated with prognosis. These four genes have the potential to become targets for STAD treatment.

Keywords: 
stomach adenocarcinoma • differentially expressed gene • ferroptosis • prognosis
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Received July 28, 2025.
Accepted August 22, 2025.
©2025 International Medical Research and Development Corporation.