Multi-omics analyses reveal interactions between GREM1+ fibroblasts and SPP1+ macrophages in gastric cancer
Abstract Gastric cancer (GC) is among the most lethal human malignancies with limited treatment options. Cell-cell interactions within the tumor microenvironment (TME) can promote tumor growth, yet their therapeutic value has not been fully explored. Here, bulk RNA-seq, single-cell RNA sequencing (s...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00967-w |
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| author | Lupeng Qiu Xiao Zhao Sheng Yao Yang Fei Yixin Gong Zishan Zhou Shunchang Jiao Jianming Xu |
| author_facet | Lupeng Qiu Xiao Zhao Sheng Yao Yang Fei Yixin Gong Zishan Zhou Shunchang Jiao Jianming Xu |
| author_sort | Lupeng Qiu |
| collection | DOAJ |
| description | Abstract Gastric cancer (GC) is among the most lethal human malignancies with limited treatment options. Cell-cell interactions within the tumor microenvironment (TME) can promote tumor growth, yet their therapeutic value has not been fully explored. Here, bulk RNA-seq, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) were integrated to analyze the heterogeneity of GC microenvironment. Tumor-specific GREM1+ fibroblasts and SPP1+ macrophages were significantly enriched in GC tissues and were involved in immunosuppression, inflammation regulation, and tumor progression. We then indicated that GREM1+ fibroblasts and SPP1+ macrophages were positively correlated in 12 independent GC datasets and validated their close localization by multiplex immunohistochemistry staining and spatial transcriptomics. Patients with both high GREM1+ fibroblasts and SPP1+ macrophages exhibited significantly shorter OS and showed enrichment of tumor-associated pathways. Our results demonstrated the complex interactions between GREM1+ fibroblasts and SPP1+ macrophages, which may serve as a potential therapeutic target for future treatment of GC. |
| format | Article |
| id | doaj-art-29688f96fa6b40ce84463d8d04b559ea |
| institution | DOAJ |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-29688f96fa6b40ce84463d8d04b559ea2025-08-20T03:10:38ZengNature Portfolionpj Precision Oncology2397-768X2025-06-019111310.1038/s41698-025-00967-wMulti-omics analyses reveal interactions between GREM1+ fibroblasts and SPP1+ macrophages in gastric cancerLupeng Qiu0Xiao Zhao1Sheng Yao2Yang Fei3Yixin Gong4Zishan Zhou5Shunchang Jiao6Jianming Xu7Department of Medical Oncology, The First Medical Centre, Chinese PLA General HospitalDepartment of Medical Oncology, The Fifth Medical Centre, Chinese PLA General HospitalDepartment of General Surgery, The First Medical Centre, Chinese PLA General HospitalDepartment of General Surgery, The First Medical Centre, Chinese PLA General HospitalResearch and Development Department, Beijing DCTY Biotech Co., Ltd.Research and Development Department, Beijing DCTY Biotech Co., Ltd.Department of Medical Oncology, The Fifth Medical Centre, Chinese PLA General HospitalDepartment of Medical Oncology, The First Medical Centre, Chinese PLA General HospitalAbstract Gastric cancer (GC) is among the most lethal human malignancies with limited treatment options. Cell-cell interactions within the tumor microenvironment (TME) can promote tumor growth, yet their therapeutic value has not been fully explored. Here, bulk RNA-seq, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics (ST) were integrated to analyze the heterogeneity of GC microenvironment. Tumor-specific GREM1+ fibroblasts and SPP1+ macrophages were significantly enriched in GC tissues and were involved in immunosuppression, inflammation regulation, and tumor progression. We then indicated that GREM1+ fibroblasts and SPP1+ macrophages were positively correlated in 12 independent GC datasets and validated their close localization by multiplex immunohistochemistry staining and spatial transcriptomics. Patients with both high GREM1+ fibroblasts and SPP1+ macrophages exhibited significantly shorter OS and showed enrichment of tumor-associated pathways. Our results demonstrated the complex interactions between GREM1+ fibroblasts and SPP1+ macrophages, which may serve as a potential therapeutic target for future treatment of GC.https://doi.org/10.1038/s41698-025-00967-w |
| spellingShingle | Lupeng Qiu Xiao Zhao Sheng Yao Yang Fei Yixin Gong Zishan Zhou Shunchang Jiao Jianming Xu Multi-omics analyses reveal interactions between GREM1+ fibroblasts and SPP1+ macrophages in gastric cancer npj Precision Oncology |
| title | Multi-omics analyses reveal interactions between GREM1+ fibroblasts and SPP1+ macrophages in gastric cancer |
| title_full | Multi-omics analyses reveal interactions between GREM1+ fibroblasts and SPP1+ macrophages in gastric cancer |
| title_fullStr | Multi-omics analyses reveal interactions between GREM1+ fibroblasts and SPP1+ macrophages in gastric cancer |
| title_full_unstemmed | Multi-omics analyses reveal interactions between GREM1+ fibroblasts and SPP1+ macrophages in gastric cancer |
| title_short | Multi-omics analyses reveal interactions between GREM1+ fibroblasts and SPP1+ macrophages in gastric cancer |
| title_sort | multi omics analyses reveal interactions between grem1 fibroblasts and spp1 macrophages in gastric cancer |
| url | https://doi.org/10.1038/s41698-025-00967-w |
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