A spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursors
Abstract Gastric cancer precursors demonstrate highly-variable rates of progression toward neoplasia. Certain high-risk precursors, such as gastric intestinal metaplasia with advanced histologic features, may be at up to 30-fold increased risk for progression compared to lower-risk intestinal metapl...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00816-w |
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| author | Robert J. Huang Ignacio A. Wichmann Andrew Su Anuja Sathe Miranda V. Shum Susan M. Grimes Rithika Meka Alison Almeda Xiangqi Bai Jeanne Shen Quan Nguyen Ingrid Luo Summer S. Han Manuel R. Amieva Joo Ha Hwang Hanlee P. Ji |
| author_facet | Robert J. Huang Ignacio A. Wichmann Andrew Su Anuja Sathe Miranda V. Shum Susan M. Grimes Rithika Meka Alison Almeda Xiangqi Bai Jeanne Shen Quan Nguyen Ingrid Luo Summer S. Han Manuel R. Amieva Joo Ha Hwang Hanlee P. Ji |
| author_sort | Robert J. Huang |
| collection | DOAJ |
| description | Abstract Gastric cancer precursors demonstrate highly-variable rates of progression toward neoplasia. Certain high-risk precursors, such as gastric intestinal metaplasia with advanced histologic features, may be at up to 30-fold increased risk for progression compared to lower-risk intestinal metaplasia. The biological differences between high- and low-risk lesions have been incompletely explored. In this study, we use several clinical cohorts to characterize the microenvironment of advanced gastric cancer precursors relative to low-risk lesions using bulk, spatial, and single-cell gene expression assays. We identified a 26-gene panel which is associated with advanced lesions, localizes to metaplastic glands on histopathology, and is expressed in aberrant mature and immature intestinal cells not normally present in the healthy stomach. This gene expression signature suggests an important role of the immature intestinal lineages in promoting carcinogenesis in the metaplastic microenvironment. These findings may help to inform future biomarker development and strategies of gastric cancer prevention. |
| format | Article |
| id | doaj-art-202b0607c6f2425a9357fb2214cdc698 |
| institution | OA Journals |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-202b0607c6f2425a9357fb2214cdc6982025-08-20T02:16:34ZengNature Portfolionpj Precision Oncology2397-768X2025-02-019111310.1038/s41698-025-00816-wA spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursorsRobert J. Huang0Ignacio A. Wichmann1Andrew Su2Anuja Sathe3Miranda V. Shum4Susan M. Grimes5Rithika Meka6Alison Almeda7Xiangqi Bai8Jeanne Shen9Quan Nguyen10Ingrid Luo11Summer S. Han12Manuel R. Amieva13Joo Ha Hwang14Hanlee P. Ji15Division of Gastroenterology, Department of Medicine, Stanford School of MedicineDivision of Oncology, Department of Medicine, Stanford School of MedicineInstitute for Molecular Bioscience, The University of QueenslandDivision of Oncology, Department of Medicine, Stanford School of MedicineDivision of Gastroenterology, Department of Medicine, Stanford School of MedicineDivision of Oncology, Department of Medicine, Stanford School of MedicineDivision of Oncology, Department of Medicine, Stanford School of MedicineDivision of Oncology, Department of Medicine, Stanford School of MedicineDivision of Oncology, Department of Medicine, Stanford School of MedicineDepartment of Pathology, Stanford School of MedicineInstitute for Molecular Bioscience, The University of QueenslandQuantitative Sciences Unit, Department of Medicine, Stanford School of MedicineQuantitative Sciences Unit, Department of Medicine, Stanford School of MedicineDepartment of Microbiology and Immunology, Stanford UniversityDivision of Gastroenterology, Department of Medicine, Stanford School of MedicineDivision of Oncology, Department of Medicine, Stanford School of MedicineAbstract Gastric cancer precursors demonstrate highly-variable rates of progression toward neoplasia. Certain high-risk precursors, such as gastric intestinal metaplasia with advanced histologic features, may be at up to 30-fold increased risk for progression compared to lower-risk intestinal metaplasia. The biological differences between high- and low-risk lesions have been incompletely explored. In this study, we use several clinical cohorts to characterize the microenvironment of advanced gastric cancer precursors relative to low-risk lesions using bulk, spatial, and single-cell gene expression assays. We identified a 26-gene panel which is associated with advanced lesions, localizes to metaplastic glands on histopathology, and is expressed in aberrant mature and immature intestinal cells not normally present in the healthy stomach. This gene expression signature suggests an important role of the immature intestinal lineages in promoting carcinogenesis in the metaplastic microenvironment. These findings may help to inform future biomarker development and strategies of gastric cancer prevention.https://doi.org/10.1038/s41698-025-00816-w |
| spellingShingle | Robert J. Huang Ignacio A. Wichmann Andrew Su Anuja Sathe Miranda V. Shum Susan M. Grimes Rithika Meka Alison Almeda Xiangqi Bai Jeanne Shen Quan Nguyen Ingrid Luo Summer S. Han Manuel R. Amieva Joo Ha Hwang Hanlee P. Ji A spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursors npj Precision Oncology |
| title | A spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursors |
| title_full | A spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursors |
| title_fullStr | A spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursors |
| title_full_unstemmed | A spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursors |
| title_short | A spatial transcriptomic signature of 26 genes resolved at single-cell resolution characterizes high-risk gastric cancer precursors |
| title_sort | spatial transcriptomic signature of 26 genes resolved at single cell resolution characterizes high risk gastric cancer precursors |
| url | https://doi.org/10.1038/s41698-025-00816-w |
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