Single‐cell sequencing reveals the role of IL‐33+ endothelial subsets in promoting early gastric cancer progression
Abstract Early gastric cancer (EGC) represents a critical stage in preventing and controlling the progression from gastritis to advanced gastric cancer (AGC). Therefore, identifying the single‐cell characteristics of EGC, particularly the cellular composition of the tumor microenvironment (TME), as...
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Wiley
2025-08-01
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| Online Access: | https://doi.org/10.1002/imt2.70050 |
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| author | Li Zhou Mei Yang Chao Deng Manqiu Hu Suhua Wu Kewen Lai Lili Zhang Zhiji Chen Qin Tang Qingliang Wang Lu Chen Runmin Zha Yuanyuan Chen Yibo Tan Song He Zhihang Zhou |
| author_facet | Li Zhou Mei Yang Chao Deng Manqiu Hu Suhua Wu Kewen Lai Lili Zhang Zhiji Chen Qin Tang Qingliang Wang Lu Chen Runmin Zha Yuanyuan Chen Yibo Tan Song He Zhihang Zhou |
| author_sort | Li Zhou |
| collection | DOAJ |
| description | Abstract Early gastric cancer (EGC) represents a critical stage in preventing and controlling the progression from gastritis to advanced gastric cancer (AGC). Therefore, identifying the single‐cell characteristics of EGC, particularly the cellular composition of the tumor microenvironment (TME), as well as identifying potential predictive markers and therapeutic targets, could significantly enhance the monitoring of gastric cancer and improve clinical cure rates. We constructed a comprehensive single‐cell RNA sequencing atlas for 184,426 high‐quality gastric cancer cells from various stages, utilizing clinical biopsies and surgical samples. Our single‐cell atlas highlights the cellular and molecular characteristics of EGC. Eight distinct cell lineage states were identified, and it was observed that the number of epithelial cell meta‐clusters gradually decreased, while the number of T&NK, B, plasma, fibroblast, myeloid, and endothelial cells increased with disease progression. Certain epithelial subclusters (metaplastic stem‐like cells (MSCs), pit mucous‐like cells (PMC‐like), proliferating cells), T‐cell subclusters (Treg, CCR7+ naive, CH25H+ CD4+, TEM CD8+, and GFPT2+ CD8+ T cells), and endothelial subclusters (IL‐33+ Venous‐1 and AMAMTSL2+ Artery‐2) were found to be increased in EGC. The Venous‐1 subcluster was found to express high levels of IL‐33. Mechanistically, it was revealed that IL‐33 enhances the survival and angiogenesis of endothelial cells by upregulating the expression of adhesion proteins CD34 and PECAM1. Patient‐derived EGC and AGC organoids were subsequently generated, and it was demonstrated that endothelial‐derived IL‐33 promoted the growth of both EGC and AGC organoids ex vitro and in vivo. Furthermore, IL‐33 was found to increase the expression of KRT17 in EGC organoids. Notably, we also found that high expression of IL‐33 was positively correlated with the depth of invasion and malignancy of EGC. This study provides novel insights into the single‐cell components involved in EGC and reveals the role of the IL‐33+ endothelial subcluster in EGC progression. |
| format | Article |
| id | doaj-art-e1f8132abcd54cb08f8f931f10352d45 |
| institution | Kabale University |
| issn | 2770-596X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | iMeta |
| spelling | doaj-art-e1f8132abcd54cb08f8f931f10352d452025-08-22T08:13:03ZengWileyiMeta2770-596X2025-08-0144n/an/a10.1002/imt2.70050Single‐cell sequencing reveals the role of IL‐33+ endothelial subsets in promoting early gastric cancer progressionLi Zhou0Mei Yang1Chao Deng2Manqiu Hu3Suhua Wu4Kewen Lai5Lili Zhang6Zhiji Chen7Qin Tang8Qingliang Wang9Lu Chen10Runmin Zha11Yuanyuan Chen12Yibo Tan13Song He14Zhihang Zhou15Department of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Pathology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Pathology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Ultrasound the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Third People's Hospital of Chengdu Chengdu ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Gastroenterology the Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaAbstract Early gastric cancer (EGC) represents a critical stage in preventing and controlling the progression from gastritis to advanced gastric cancer (AGC). Therefore, identifying the single‐cell characteristics of EGC, particularly the cellular composition of the tumor microenvironment (TME), as well as identifying potential predictive markers and therapeutic targets, could significantly enhance the monitoring of gastric cancer and improve clinical cure rates. We constructed a comprehensive single‐cell RNA sequencing atlas for 184,426 high‐quality gastric cancer cells from various stages, utilizing clinical biopsies and surgical samples. Our single‐cell atlas highlights the cellular and molecular characteristics of EGC. Eight distinct cell lineage states were identified, and it was observed that the number of epithelial cell meta‐clusters gradually decreased, while the number of T&NK, B, plasma, fibroblast, myeloid, and endothelial cells increased with disease progression. Certain epithelial subclusters (metaplastic stem‐like cells (MSCs), pit mucous‐like cells (PMC‐like), proliferating cells), T‐cell subclusters (Treg, CCR7+ naive, CH25H+ CD4+, TEM CD8+, and GFPT2+ CD8+ T cells), and endothelial subclusters (IL‐33+ Venous‐1 and AMAMTSL2+ Artery‐2) were found to be increased in EGC. The Venous‐1 subcluster was found to express high levels of IL‐33. Mechanistically, it was revealed that IL‐33 enhances the survival and angiogenesis of endothelial cells by upregulating the expression of adhesion proteins CD34 and PECAM1. Patient‐derived EGC and AGC organoids were subsequently generated, and it was demonstrated that endothelial‐derived IL‐33 promoted the growth of both EGC and AGC organoids ex vitro and in vivo. Furthermore, IL‐33 was found to increase the expression of KRT17 in EGC organoids. Notably, we also found that high expression of IL‐33 was positively correlated with the depth of invasion and malignancy of EGC. This study provides novel insights into the single‐cell components involved in EGC and reveals the role of the IL‐33+ endothelial subcluster in EGC progression.https://doi.org/10.1002/imt2.70050angiogenesisearly gastric cancerendothelial cellsIL‐33tumor microenvironmentorganoids |
| spellingShingle | Li Zhou Mei Yang Chao Deng Manqiu Hu Suhua Wu Kewen Lai Lili Zhang Zhiji Chen Qin Tang Qingliang Wang Lu Chen Runmin Zha Yuanyuan Chen Yibo Tan Song He Zhihang Zhou Single‐cell sequencing reveals the role of IL‐33+ endothelial subsets in promoting early gastric cancer progression iMeta angiogenesis early gastric cancer endothelial cells IL‐33 tumor microenvironment organoids |
| title | Single‐cell sequencing reveals the role of IL‐33+ endothelial subsets in promoting early gastric cancer progression |
| title_full | Single‐cell sequencing reveals the role of IL‐33+ endothelial subsets in promoting early gastric cancer progression |
| title_fullStr | Single‐cell sequencing reveals the role of IL‐33+ endothelial subsets in promoting early gastric cancer progression |
| title_full_unstemmed | Single‐cell sequencing reveals the role of IL‐33+ endothelial subsets in promoting early gastric cancer progression |
| title_short | Single‐cell sequencing reveals the role of IL‐33+ endothelial subsets in promoting early gastric cancer progression |
| title_sort | single cell sequencing reveals the role of il 33 endothelial subsets in promoting early gastric cancer progression |
| topic | angiogenesis early gastric cancer endothelial cells IL‐33 tumor microenvironment organoids |
| url | https://doi.org/10.1002/imt2.70050 |
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