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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Metabolism
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1499580
This article is part of the Research Topic Metabolic Crosstalk between Cancer Cells and Immune Cells in the Tumor Microenvironment: Cellular and Molecular Insights, and their Therapeutic Implications View all 10 articles

Integrative Analysis of Ferroptosis in the Hypoxic Microenvironment of Gastric Cancer Unveils the Immune Landscape and Personalized Therapeutic Strategies

Provisionally accepted
Xiao Xu Xiao Xu 1Liangling Fa Liangling Fa 2*Dong Jigang Dong Jigang 1,3Xiaoxiao Sun Xiaoxiao Sun 1*Fangfang Yang Fangfang Yang 4Yongrui Liu Yongrui Liu 5*Jifu Song Jifu Song 1*Yongli Zhao Yongli Zhao 1*
  • 1 Department of Radiation Oncology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, China
  • 2 Department of Pathology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, Shandong Province, China
  • 3 Tianjin Medical University, Tianjin, Tianjin Municipality, China
  • 4 Cancer Precision Medical Center, Qingdao University, Qingdao, China
  • 5 Department of Oncology, Linyi Cancer Hospital, Linyi, Shandong Province, China

The final, formatted version of the article will be published soon.

    Background: Ferroptosis is a cell death mode caused by excessive accumulation of lipid peroxides caused by disturbance of intracellular metabolic pathway, which is closely related to iron and cholesterol metabolism homeostasis. Its regulation within the hypoxic metabolic tumor microenvironment (TME) has the potential to improve the effectiveness of tumor immunotherapy. The predictive role of ferroptosis in gastric cancer (GC) hypoxia TME, particularly in relation to TME immune cell infiltration, has not been fully explained. Methods: By analyzing the mRNA expression data of ferroptosis and hypoxia-related genes, a prediction model was constructed to evaluate further the predictive value of immune cell infiltration, clinical characteristics, and immunotherapy efficacy of gastric cancer, and the essential genes were validated.Results: Two distinct molecular states of ferroptosis-hypoxia were identified in GC. Notably, patients with high ferroptosis-hypoxia risk scores (FHRS) displayed significant levels of hypoxia and epithelial-mesenchymal transition (EMT), which were associated with unfavorable prognosis, increased chemoresistance, and heightened immunosuppression.This study demonstrates that ferroptosis under hypoxic conditions significantly affects the modulation of the tumor immune microenvironment. The FHRS can independently predict prognosis in gastric cancer. Assessing the molecular status of ferroptosis-hypoxia in individual patients will help in selecting more suitable immunotherapy regimens by providing a better understanding of TME characteristics and predicting immunotherapeutic outcomes.

    Keywords: ferroptosis, Immune landscape, Immunotherapy, Hypoxia microenvironment, tumor metabolism

    Received: 21 Sep 2024; Accepted: 06 Dec 2024.

    Copyright: © 2024 Xu, Fa, Jigang, Sun, Yang, Liu, Song and Zhao. 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:
    Liangling Fa, Department of Pathology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, Shandong Province, China
    Xiaoxiao Sun, Department of Radiation Oncology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, China
    Yongrui Liu, Department of Oncology, Linyi Cancer Hospital, Linyi, Shandong Province, China
    Jifu Song, Department of Radiation Oncology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, China
    Yongli Zhao, Department of Radiation Oncology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.