Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progression
Abstract Background Single-cell transcription data provided unprecedented molecular information, enabling us to directly encode the ecosystem of colorectal cancer (CRC). Characterization of the diversity of epithelial cells and how they cooperate with tumor microenvironment cells (TME) to endow CRC...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03661-8 |
| _version_ | 1811226731232624640 |
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| author | Rongfang Shen Ping Li Botao Zhang Lin Feng Shujun Cheng |
| author_facet | Rongfang Shen Ping Li Botao Zhang Lin Feng Shujun Cheng |
| author_sort | Rongfang Shen |
| collection | DOAJ |
| description | Abstract Background Single-cell transcription data provided unprecedented molecular information, enabling us to directly encode the ecosystem of colorectal cancer (CRC). Characterization of the diversity of epithelial cells and how they cooperate with tumor microenvironment cells (TME) to endow CRC with aggressive characteristics at single-cell resolution is critical for the understanding of tumor progression mechanism. Methods In this study, we comprehensively analyzed the single-cell transcription data, bulk-RNA sequencing data and pathological tissue data. In detail, cellular heterogeneity of TME and epithelial cells were analyzed by unsupervised classification and consensus nonnegative matrix factorization analysis, respectively. Functional status of epithelial clusters was annotated by CancerSEA and its crosstalk with TME cells was investigated using CellPhoneDB and correlation analysis. Findings from single-cell transcription data were further validated in bulk-RNA sequencing data and pathological tissue data. Results A distinct cellular composition was observed between tumor and normal tissues, and tumors exhibited immunosuppressive phenotypes. Regarding epithelial cells, we identified one highly invasiveQuery cluster, C4, that correlated closely with tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). Further analysis emphasized the TAMs subclass TAM1 and CAFs subclass S5 are closely related with C4. Conclusions In summary, our study elaborates on the cellular heterogeneity of CRC, revealing that TAMs and CAFs were critical for crosstalk network epithelial cells and TME cells. This in-depth understanding of cancer cell-TME network provided theoretical basis for the development of new drugs targeting this sophisticated network in CRC. |
| first_indexed | 2024-04-12T09:30:15Z |
| format | Article |
| id | doaj.art-662d745afb694ad5b99d29de2dcffc84 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T09:30:15Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-662d745afb694ad5b99d29de2dcffc842022-12-22T03:38:22ZengBMCJournal of Translational Medicine1479-58762022-10-0120111910.1186/s12967-022-03661-8Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progressionRongfang Shen0Ping Li1Botao Zhang2Lin Feng3Shujun Cheng4State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeMedical Oncology Department, Pediatric Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing Key Laboratory of Pediatric Hematology Oncology, Key Laboratory of Major Diseases in Children, Ministry of EducationDepartment of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical UniversityState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background Single-cell transcription data provided unprecedented molecular information, enabling us to directly encode the ecosystem of colorectal cancer (CRC). Characterization of the diversity of epithelial cells and how they cooperate with tumor microenvironment cells (TME) to endow CRC with aggressive characteristics at single-cell resolution is critical for the understanding of tumor progression mechanism. Methods In this study, we comprehensively analyzed the single-cell transcription data, bulk-RNA sequencing data and pathological tissue data. In detail, cellular heterogeneity of TME and epithelial cells were analyzed by unsupervised classification and consensus nonnegative matrix factorization analysis, respectively. Functional status of epithelial clusters was annotated by CancerSEA and its crosstalk with TME cells was investigated using CellPhoneDB and correlation analysis. Findings from single-cell transcription data were further validated in bulk-RNA sequencing data and pathological tissue data. Results A distinct cellular composition was observed between tumor and normal tissues, and tumors exhibited immunosuppressive phenotypes. Regarding epithelial cells, we identified one highly invasiveQuery cluster, C4, that correlated closely with tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). Further analysis emphasized the TAMs subclass TAM1 and CAFs subclass S5 are closely related with C4. Conclusions In summary, our study elaborates on the cellular heterogeneity of CRC, revealing that TAMs and CAFs were critical for crosstalk network epithelial cells and TME cells. This in-depth understanding of cancer cell-TME network provided theoretical basis for the development of new drugs targeting this sophisticated network in CRC.https://doi.org/10.1186/s12967-022-03661-8Colorectal cancerscRNA-seqTumor heterogeneityEpithelium-microenvironment communicationTumor-associated macrophagesCancer-associated fibroblasts |
| spellingShingle | Rongfang Shen Ping Li Botao Zhang Lin Feng Shujun Cheng Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progression Journal of Translational Medicine Colorectal cancer scRNA-seq Tumor heterogeneity Epithelium-microenvironment communication Tumor-associated macrophages Cancer-associated fibroblasts |
| title | Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progression |
| title_full | Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progression |
| title_fullStr | Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progression |
| title_full_unstemmed | Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progression |
| title_short | Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progression |
| title_sort | decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells tams and cafsin tumor progression |
| topic | Colorectal cancer scRNA-seq Tumor heterogeneity Epithelium-microenvironment communication Tumor-associated macrophages Cancer-associated fibroblasts |
| url | https://doi.org/10.1186/s12967-022-03661-8 |
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