ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1643235
This article is part of the Research TopicAdvancing Biomarker Discovery, Molecular Mechanisms, and Immunological Insights in Tumor Precision MedicineView all 5 articles
Ferroptosis's Master Switch GPX4 Emerges as Universal Biomarker for Precision Immunotherapy: A Pan-cancer Study with in vitro experiments validation
Provisionally accepted
- Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
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Glutathione peroxidase 4 (GPX4) is a key enzyme in ferroptosis. Gaining insight into GPX4's mechanisms and biological roles could offer valuable therapeutic insights for cancer treatment. Through analysis of various bioinformatics resources such as The Cancer Genome Atlas (TCGA), GEPIA2, and cBioPortal, we observed that GPX4 was upregulated in several cancer types. Its potential as a diagnostic biomarker was confirmed by its high reliability in differentiating cancerous from normal tissues, with AUC values surpassing 0.8 in multiple cancers. Functional studies verified its oncogenic function in colorectal and gastric cancer cell lines. In terms of prognosis, GPX4 expression levels were closely associated with overall survival across various cancers. Furthermore, we detected a correlation between the mutation burden of GPX4 across different types of cancer and patient survival outcomes. Additionally, immune infiltration analysis showed significant correlations between GPX4 expression and immune cell presence, particularly macrophages and M2 type macrophages. GPX4 expression also correlated highly with immune modulator pathways and checkpoints. Collectively, these pan-cancer analyses underscore the potential of GPX4 as a This is a provisional file, not the final typeset article therapeutic target and biomarker in multiple cancers. Further in-depth studies on GPX4's regulatory mechanisms and clinicopathological significance are warranted to develop novel therapies for the prevention and treatment of human tumors.
Keywords: glutathione peroxidase 4, ferroptosis, Pan-cancer, Immunotherapy, Tumor Microenvironment
Received: 08 Jun 2025; Accepted: 23 Sep 2025.
Copyright: © 2025 Li, Zhu and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ruihua Dong, ruihua_dong_rw@163.com
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