Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells
Abstract The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcrip...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04600-x |
| _version_ | 1797629998998224896 |
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| author | Muhong Wang Chunyu Deng Cheng Yang Mingze Yan Haibo Lu Yan Zhang Honghao Liu Zhekuan Tong Jiaao Ma Jiaming Wang Yan Zhang Jiahao Wang Yuhong Xuan Haiyue Cheng Kai Zhao Jiaqi Zhang Cuicui Chai Mingzhe Li Zhiwei Yu |
| author_facet | Muhong Wang Chunyu Deng Cheng Yang Mingze Yan Haibo Lu Yan Zhang Honghao Liu Zhekuan Tong Jiaao Ma Jiaming Wang Yan Zhang Jiahao Wang Yuhong Xuan Haiyue Cheng Kai Zhao Jiaqi Zhang Cuicui Chai Mingzhe Li Zhiwei Yu |
| author_sort | Muhong Wang |
| collection | DOAJ |
| description | Abstract The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples. Graphical Abstract |
| first_indexed | 2024-03-11T11:00:47Z |
| format | Article |
| id | doaj.art-0543f535e4cf499fa131440c24b44154 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-11T11:00:47Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-0543f535e4cf499fa131440c24b441542023-11-12T12:28:41ZengBMCJournal of Translational Medicine1479-58762023-11-0121111610.1186/s12967-023-04600-xUnraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cellsMuhong Wang0Chunyu Deng1Cheng Yang2Mingze Yan3Haibo Lu4Yan Zhang5Honghao Liu6Zhekuan Tong7Jiaao Ma8Jiaming Wang9Yan Zhang10Jiahao Wang11Yuhong Xuan12Haiyue Cheng13Kai Zhao14Jiaqi Zhang15Cuicui Chai16Mingzhe Li17Zhiwei Yu18Department of Colorectal Surgery, Harbin Medical University Cancer HospitalSchool of Life Science and Technology, Harbin Institute of TechnologyDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalSchool of Life Science and Technology, Harbin Institute of TechnologySchool of Life Science and Technology, Harbin Institute of TechnologyDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalDigestive Disease Center, The Seventh Affiliated Hospital Sun Yat-Sen UniversityDigestive Disease Center, The Seventh Affiliated Hospital Sun Yat-Sen UniversityDepartment of Colorectal Surgery, Harbin Medical University Cancer HospitalAbstract The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples. Graphical Abstracthttps://doi.org/10.1186/s12967-023-04600-xColorectal cancerSingle-cell RNA-seqSpatial transcriptomicsTumor immune microenvironmentEpithelial-mesenchymal transition (EMT) |
| spellingShingle | Muhong Wang Chunyu Deng Cheng Yang Mingze Yan Haibo Lu Yan Zhang Honghao Liu Zhekuan Tong Jiaao Ma Jiaming Wang Yan Zhang Jiahao Wang Yuhong Xuan Haiyue Cheng Kai Zhao Jiaqi Zhang Cuicui Chai Mingzhe Li Zhiwei Yu Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells Journal of Translational Medicine Colorectal cancer Single-cell RNA-seq Spatial transcriptomics Tumor immune microenvironment Epithelial-mesenchymal transition (EMT) |
| title | Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells |
| title_full | Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells |
| title_fullStr | Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells |
| title_full_unstemmed | Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells |
| title_short | Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells |
| title_sort | unraveling temporal and spatial biomarkers of epithelial mesenchymal transition in colorectal cancer insights into the crucial role of immunosuppressive cells |
| topic | Colorectal cancer Single-cell RNA-seq Spatial transcriptomics Tumor immune microenvironment Epithelial-mesenchymal transition (EMT) |
| url | https://doi.org/10.1186/s12967-023-04600-x |
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