Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies
Abstract Background The metabolism of stearoyl-GPE plays a key role in the liver metastasis of gastric cancer. This investigation delves into the mechanisms underlying the intricate tumor microenvironment (TME) heterogeneity triggered by stearoyl metabolism in gastric cancer with liver metastasis (L...
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| Format: | Article |
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Springer
2025-01-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-01769-z |
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| author | Zhongqiu Yang Yuquan Chen Yaping Miao Haisheng Yan Kexin Chen Yaoqin Xu Lanqian Su Lanyue Zhang Yalan Yan Hao Chi Jin Fu Lexin Wang |
| author_facet | Zhongqiu Yang Yuquan Chen Yaping Miao Haisheng Yan Kexin Chen Yaoqin Xu Lanqian Su Lanyue Zhang Yalan Yan Hao Chi Jin Fu Lexin Wang |
| author_sort | Zhongqiu Yang |
| collection | DOAJ |
| description | Abstract Background The metabolism of stearoyl-GPE plays a key role in the liver metastasis of gastric cancer. This investigation delves into the mechanisms underlying the intricate tumor microenvironment (TME) heterogeneity triggered by stearoyl metabolism in gastric cancer with liver metastasis (LMGC), offering novel perspectives for LMGC. Objective Utilizing Mendelian randomization, we determined that stearoyl metabolism significantly contributes to the progression of gastric cancer (GC). Following this, bulk transcriptome analyses and single-cell multiomics techniques to investigate the roles of stearoyl-GPE metabolism-related genes, particularly NCOA4, in regulating LMGC TME. Results Our analysis highlights the crucial role of stearoyl metabolism in modulating the complex microenvironment of LMGC, particularly impacting monocyte cells. Through single-cell sequencing and spatial transcriptomics, we have identified key metabolic genes specific to stearoyl metabolism within the monocyte cell population, including NCOA4. Regarding the relationship between ferroptosis, stearoyl metabolism, and LMGC findings, it is plausible that stearoyl metabolism and LMGC pathways intersect with mechanisms involved in ferroptosis. Ferroptosis, characterized by iron-dependent lipid peroxidation, represents a regulated form of cell death. The activity of Stearoyl-CoA desaturase (SCD), a critical enzyme in stearoyl metabolism, has been associated with the modulation of lipid composition and susceptibility to ferroptosis. Furthermore, the LMGC is integral to cellular processes related to oxidative stress and lipid metabolism, both of which are significant factors in the context of ferroptosis. Conclusion This study enhances the understanding of the relationship between stearoyl metabolism and ferroptosis in promoting liver metastasis of gastric cancer and its role in the regulation of tumor heterogeneity. In addition, this study contributes to a deeper understanding of the dynamics of gastric cancer tumor microenvironment (TME) and provides a basis for the development of better interventions to combat cancer metastasis. |
| format | Article |
| id | doaj-art-ae5da8ea0dbe4df6a0e1e81ce8f3a944 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-ae5da8ea0dbe4df6a0e1e81ce8f3a9442025-01-19T12:29:23ZengSpringerDiscover Oncology2730-60112025-01-0116112110.1007/s12672-025-01769-zElucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategiesZhongqiu Yang0Yuquan Chen1Yaping Miao2Haisheng Yan3Kexin Chen4Yaoqin Xu5Lanqian Su6Lanyue Zhang7Yalan Yan8Hao Chi9Jin Fu10Lexin Wang11Department of General Surgery, Dazhou Central HospitalSchool of Public Health and Preventive Medicine, Faculty of Medicine, Nursing & Health Sciences, Monash UniversityGeneral Hospital of Ningxia Medical UniversityGeneral Hospital of Ningxia Medical UniversityGeneral Hospital of Ningxia Medical UniversityGeneral Hospital of Ningxia Medical UniversitySchool of Clinical Medicine, Affiliated Hospital of Southwest Medical UniversitySchool of Clinical Medicine, Affiliated Hospital of Southwest Medical UniversitySchool of Clinical Medicine, Affiliated Hospital of Southwest Medical UniversitySchool of Clinical Medicine, Affiliated Hospital of Southwest Medical UniversityDepartment of Laboratory Medicine, Chonggang General HospitalWestern Institute of Digital-Intelligent MedicineAbstract Background The metabolism of stearoyl-GPE plays a key role in the liver metastasis of gastric cancer. This investigation delves into the mechanisms underlying the intricate tumor microenvironment (TME) heterogeneity triggered by stearoyl metabolism in gastric cancer with liver metastasis (LMGC), offering novel perspectives for LMGC. Objective Utilizing Mendelian randomization, we determined that stearoyl metabolism significantly contributes to the progression of gastric cancer (GC). Following this, bulk transcriptome analyses and single-cell multiomics techniques to investigate the roles of stearoyl-GPE metabolism-related genes, particularly NCOA4, in regulating LMGC TME. Results Our analysis highlights the crucial role of stearoyl metabolism in modulating the complex microenvironment of LMGC, particularly impacting monocyte cells. Through single-cell sequencing and spatial transcriptomics, we have identified key metabolic genes specific to stearoyl metabolism within the monocyte cell population, including NCOA4. Regarding the relationship between ferroptosis, stearoyl metabolism, and LMGC findings, it is plausible that stearoyl metabolism and LMGC pathways intersect with mechanisms involved in ferroptosis. Ferroptosis, characterized by iron-dependent lipid peroxidation, represents a regulated form of cell death. The activity of Stearoyl-CoA desaturase (SCD), a critical enzyme in stearoyl metabolism, has been associated with the modulation of lipid composition and susceptibility to ferroptosis. Furthermore, the LMGC is integral to cellular processes related to oxidative stress and lipid metabolism, both of which are significant factors in the context of ferroptosis. Conclusion This study enhances the understanding of the relationship between stearoyl metabolism and ferroptosis in promoting liver metastasis of gastric cancer and its role in the regulation of tumor heterogeneity. In addition, this study contributes to a deeper understanding of the dynamics of gastric cancer tumor microenvironment (TME) and provides a basis for the development of better interventions to combat cancer metastasis.https://doi.org/10.1007/s12672-025-01769-zLMGCFerroptosisStearoyl metabolismNCOA4Spatial transcriptomicsSingle-cell RNA sequencing |
| spellingShingle | Zhongqiu Yang Yuquan Chen Yaping Miao Haisheng Yan Kexin Chen Yaoqin Xu Lanqian Su Lanyue Zhang Yalan Yan Hao Chi Jin Fu Lexin Wang Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies Discover Oncology LMGC Ferroptosis Stearoyl metabolism NCOA4 Spatial transcriptomics Single-cell RNA sequencing |
| title | Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies |
| title_full | Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies |
| title_fullStr | Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies |
| title_full_unstemmed | Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies |
| title_short | Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies |
| title_sort | elucidating stearoyl metabolism and ncoa4 mediated ferroptosis in gastric cancer liver metastasis through multi omics single cell integrative mendelian analysis advancing personalized immunotherapy strategies |
| topic | LMGC Ferroptosis Stearoyl metabolism NCOA4 Spatial transcriptomics Single-cell RNA sequencing |
| url | https://doi.org/10.1007/s12672-025-01769-z |
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