Spatial transcriptomics unravels the interactive network of aflatoxin B1-driven gastric cancer: Multi-omics integration of transcriptome and mendelian randomization
The escalating threat of widespread exposure to environmental pollutants on human health has drawn increasing attention, particularly regarding mycotoxin contaminants with potent carcinogenic properties. As a prototypical environmental toxin, the molecular mechanisms underlying aflatoxin B1-induced...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325012643 |
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| author | Yong-Le Li Cong Liu Meng Tang Wan-Shou Wei Xiao-Mei Xie Yuan Gan Xuan-Hua Chen Shan-Shan Dong Li-He Jiang |
| author_facet | Yong-Le Li Cong Liu Meng Tang Wan-Shou Wei Xiao-Mei Xie Yuan Gan Xuan-Hua Chen Shan-Shan Dong Li-He Jiang |
| author_sort | Yong-Le Li |
| collection | DOAJ |
| description | The escalating threat of widespread exposure to environmental pollutants on human health has drawn increasing attention, particularly regarding mycotoxin contaminants with potent carcinogenic properties. As a prototypical environmental toxin, the molecular mechanisms underlying aflatoxin B1-induced gastric carcinogenesis remain poorly defined. This study systematically elucidates the molecular network through which aflatoxin B1 (AFB1) synergistically drives the malignant progression of gastric cancer by specifically targeting five core regulatory genes, exemplified by its upregulation of cyclin genes CCNE1 and CCNE2. Molecular docking simulations demonstrate significant binding activity between AFB1 and the core targets, with MAPK3 exhibiting the optimal binding affinity as evidenced by the most favorable binding free energy. Integrated single-cell RNA sequencing of human gastric cancer tissues and spatial transcriptomics (10X Visium) revealed cell-type-specific expression patterns of these core target genes within immune cell clusters in the tumor microenvironment, particularly in T cell subpopulations. Innovatively, this study constructs a multi-layered molecular regulatory map of AFB1-induced gastric carcinogenesis, establishing a novel paradigm for multi-omics integration in elucidating the toxicological mechanisms of environmental carcinogens. |
| format | Article |
| id | doaj-art-158939d6f83b4ed293e5ccde9f14205f |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-158939d6f83b4ed293e5ccde9f14205f2025-08-25T04:13:57ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130311891910.1016/j.ecoenv.2025.118919Spatial transcriptomics unravels the interactive network of aflatoxin B1-driven gastric cancer: Multi-omics integration of transcriptome and mendelian randomizationYong-Le Li0Cong Liu1Meng Tang2Wan-Shou Wei3Xiao-Mei Xie4Yuan Gan5Xuan-Hua Chen6Shan-Shan Dong7Li-He Jiang8School of Clinical Medicine, School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, ChinaChongqing Key Laboratory of Prevention and Treatment for Occupational Diseases and Poisoning, The First Affiliated Hospital of Chongqing Medical and pharmaceutical College, Chongqing 400060, ChinaSchool of Clinical Medicine, School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, ChinaSchool of Clinical Medicine, School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, ChinaSchool of Clinical Medicine, School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, ChinaSchool of Clinical Medicine, School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, ChinaSchool of Clinical Medicine, School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, ChinaSchool of Clinical Medicine, School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, ChinaSchool of Clinical Medicine, School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China; Ministry of Education, Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University), Nanning, Guangxi 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University), Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi 541199, China; Correspondence to: School of Basic Medical Sciences, Youjiang Medical University for Nationalities, No. 98 Chengxiang Road, Youjiang District, Baise, Guangxi 533000, China.The escalating threat of widespread exposure to environmental pollutants on human health has drawn increasing attention, particularly regarding mycotoxin contaminants with potent carcinogenic properties. As a prototypical environmental toxin, the molecular mechanisms underlying aflatoxin B1-induced gastric carcinogenesis remain poorly defined. This study systematically elucidates the molecular network through which aflatoxin B1 (AFB1) synergistically drives the malignant progression of gastric cancer by specifically targeting five core regulatory genes, exemplified by its upregulation of cyclin genes CCNE1 and CCNE2. Molecular docking simulations demonstrate significant binding activity between AFB1 and the core targets, with MAPK3 exhibiting the optimal binding affinity as evidenced by the most favorable binding free energy. Integrated single-cell RNA sequencing of human gastric cancer tissues and spatial transcriptomics (10X Visium) revealed cell-type-specific expression patterns of these core target genes within immune cell clusters in the tumor microenvironment, particularly in T cell subpopulations. Innovatively, this study constructs a multi-layered molecular regulatory map of AFB1-induced gastric carcinogenesis, establishing a novel paradigm for multi-omics integration in elucidating the toxicological mechanisms of environmental carcinogens.http://www.sciencedirect.com/science/article/pii/S0147651325012643Environmental pollutants；Mycotoxins；Aflatoxin B1；Gastric cancer； Multi-omics；Mendelian randomization；Immune microenvironment |
| spellingShingle | Yong-Le Li Cong Liu Meng Tang Wan-Shou Wei Xiao-Mei Xie Yuan Gan Xuan-Hua Chen Shan-Shan Dong Li-He Jiang Spatial transcriptomics unravels the interactive network of aflatoxin B1-driven gastric cancer: Multi-omics integration of transcriptome and mendelian randomization Ecotoxicology and Environmental Safety Environmental pollutants；Mycotoxins；Aflatoxin B1；Gastric cancer； Multi-omics；Mendelian randomization；Immune microenvironment |
| title | Spatial transcriptomics unravels the interactive network of aflatoxin B1-driven gastric cancer: Multi-omics integration of transcriptome and mendelian randomization |
| title_full | Spatial transcriptomics unravels the interactive network of aflatoxin B1-driven gastric cancer: Multi-omics integration of transcriptome and mendelian randomization |
| title_fullStr | Spatial transcriptomics unravels the interactive network of aflatoxin B1-driven gastric cancer: Multi-omics integration of transcriptome and mendelian randomization |
| title_full_unstemmed | Spatial transcriptomics unravels the interactive network of aflatoxin B1-driven gastric cancer: Multi-omics integration of transcriptome and mendelian randomization |
| title_short | Spatial transcriptomics unravels the interactive network of aflatoxin B1-driven gastric cancer: Multi-omics integration of transcriptome and mendelian randomization |
| title_sort | spatial transcriptomics unravels the interactive network of aflatoxin b1 driven gastric cancer multi omics integration of transcriptome and mendelian randomization |
| topic | Environmental pollutants；Mycotoxins；Aflatoxin B1；Gastric cancer； Multi-omics；Mendelian randomization；Immune microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325012643 |
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