Integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategies
BackgroundFerroptosis 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) h...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1499580/full |
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| author | Xiao Xu Liangling Fa Xiaoxiao Sun Fangfang Yang Yongrui Liu Jifu Song Yongli Zhao Jigang Dong Jigang Dong |
| author_facet | Xiao Xu Liangling Fa Xiaoxiao Sun Fangfang Yang Yongrui Liu Jifu Song Yongli Zhao Jigang Dong Jigang Dong |
| author_sort | Xiao Xu |
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| description | BackgroundFerroptosis 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.MethodsBy 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.ResultsTwo 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.ConclusionsThis 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. |
| format | Article |
| id | doaj-art-ef677d61b9a54ae280ce52dcc95f289a |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-ef677d61b9a54ae280ce52dcc95f289a2025-01-13T05:10:46ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.14995801499580Integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategiesXiao Xu0Liangling Fa1Xiaoxiao Sun2Fangfang Yang3Yongrui Liu4Jifu Song5Yongli Zhao6Jigang Dong7Jigang Dong8Department of Radiation Oncology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, ChinaDepartment of Pathology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, ChinaDepartment of Radiation Oncology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, ChinaCancer Precision Medical Center, Qingdao University, Qingdao, ChinaDepartment of Oncology, Linyi Cancer Hospital, Linyi, ChinaDepartment of Radiation Oncology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, ChinaDepartment of Radiation Oncology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, ChinaDepartment of Radiation Oncology, Qingdao People’s Hospital Group (Jiaozhou), Jiaozhou Central Hospital of Qingdao, Qingdao, ChinaTianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, ChinaBackgroundFerroptosis 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.MethodsBy 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.ResultsTwo 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.ConclusionsThis 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.https://www.frontiersin.org/articles/10.3389/fonc.2024.1499580/fullferroptosisimmune landscapeimmunotherapyhypoxia microenvironmenttumor metabolism |
| spellingShingle | Xiao Xu Liangling Fa Xiaoxiao Sun Fangfang Yang Yongrui Liu Jifu Song Yongli Zhao Jigang Dong Jigang Dong Integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategies Frontiers in Oncology ferroptosis immune landscape immunotherapy hypoxia microenvironment tumor metabolism |
| title | Integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategies |
| title_full | Integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategies |
| title_fullStr | Integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategies |
| title_full_unstemmed | Integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategies |
| title_short | Integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategies |
| title_sort | integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategies |
| topic | ferroptosis immune landscape immunotherapy hypoxia microenvironment tumor metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1499580/full |
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