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Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies.

作者信息

Yang Zhongqiu, Chen Yuquan, Miao Yaping, Yan Haisheng, Chen Kexin, Xu Yaoqin, Su Lanqian, Zhang Lanyue, Yan Yalan, Chi Hao, Fu Jin, Wang Lexin

机构信息

Department of General Surgery, Dazhou Central Hospital, Dazhou, 635000, China.

School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing & Health Sciences, Monash University, Victoria, 3004, Australia.

出版信息

Discov Oncol. 2025 Jan 15;16(1):46. doi: 10.1007/s12672-025-01769-z.

DOI:10.1007/s12672-025-01769-z
PMID:39812999
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11735723/
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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/568da03f586a/12672_2025_1769_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/43eba638f90b/12672_2025_1769_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/b94aee8619f4/12672_2025_1769_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/9c58a4e741f4/12672_2025_1769_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/5037cd810b3a/12672_2025_1769_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/3a53efcaa155/12672_2025_1769_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/703134624c6d/12672_2025_1769_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/26fd2101c96c/12672_2025_1769_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/a60541ee3164/12672_2025_1769_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/350edde73de3/12672_2025_1769_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/568da03f586a/12672_2025_1769_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/43eba638f90b/12672_2025_1769_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/b94aee8619f4/12672_2025_1769_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/9c58a4e741f4/12672_2025_1769_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/5037cd810b3a/12672_2025_1769_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/3a53efcaa155/12672_2025_1769_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/703134624c6d/12672_2025_1769_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/26fd2101c96c/12672_2025_1769_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/a60541ee3164/12672_2025_1769_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/350edde73de3/12672_2025_1769_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87b4/11735723/568da03f586a/12672_2025_1769_Fig10_HTML.jpg

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[2]
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[4]
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[5]
ATP6AP1 drives pyroptosis-mediated immune evasion in hepatocellular carcinoma: a machine learning-guided therapeutic target.

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本文引用的文献

[1]
CXC chemokine receptor 4 - mediated immune modulation and tumor microenvironment heterogeneity in gastric cancer: Utilizing multi-omics approaches to identify potential therapeutic targets.

Biofactors. 2025

[2]
Integrative biomarker discovery and immune profiling for ulcerative colitis: a multi-methodological approach.

Sci Rep. 2024-10-16

[3]
Revealing the association between East Asian oral microbiome and colorectal cancer through Mendelian randomization and multi-omics analysis.

Front Cell Infect Microbiol. 2024-9-17

[4]
Deciphering the role of tryptophan metabolism-associated genes ECHS1 and ALDH2 in gastric cancer: implications for tumor immunity and personalized therapy.

Front Immunol. 2024

[5]
Deciphering the impact of aggregated autophagy-related genes TUBA1B and HSP90AA1 on colorectal cancer evolution: a single-cell sequencing study of the tumor microenvironment.

Discov Oncol. 2024-9-11

[6]
Role of glycosylation-related gene MGAT1 in pancreatic ductal adenocarcinoma.

Front Immunol. 2024

[7]
Unravelling infiltrating T-cell heterogeneity in kidney renal clear cell carcinoma: Integrative single-cell and spatial transcriptomic profiling.

J Cell Mol Med. 2024-6

[8]
Deciphering the tumour microenvironment of clear cell renal cell carcinoma: Prognostic insights from programmed death genes using machine learning.

J Cell Mol Med. 2024-7

[9]
Mitophagy and clear cell renal cell carcinoma: insights from single-cell and spatial transcriptomics analysis.

Front Immunol. 2024

[10]
Causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomisation study.

J Cancer. 2024-6-3

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