Single-cell transcriptomes of dissecting the intra-tumoral heterogeneity of breast cancer microenvironment
Abstract Objective To investigate the mechanism by which heterogeneity in breast cancer developed and acted in single-cell transcriptomes. Methods The composition of breast cancer based on the single-cell transcriptomes of 54,055 high-quality cells from clinical specimens of 4 malignant and 4 non-ma...
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| Format: | Article |
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Springer
2024-12-01
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| Series: | Journal of Cancer Research and Clinical Oncology |
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| Online Access: | https://doi.org/10.1007/s00432-024-06015-7 |
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| author | Peixian Chen Kaifeng Liang Xiaofan Mao Qiuyuan Wu Zhiyan Chen Yabin Jin Kairong Lin Tiancheng He Shuqing Yang Huiqi Huang Guolin Ye Juntao Gao Dan Zhou Zhihao Zeng |
| author_facet | Peixian Chen Kaifeng Liang Xiaofan Mao Qiuyuan Wu Zhiyan Chen Yabin Jin Kairong Lin Tiancheng He Shuqing Yang Huiqi Huang Guolin Ye Juntao Gao Dan Zhou Zhihao Zeng |
| author_sort | Peixian Chen |
| collection | DOAJ |
| description | Abstract Objective To investigate the mechanism by which heterogeneity in breast cancer developed and acted in single-cell transcriptomes. Methods The composition of breast cancer based on the single-cell transcriptomes of 54,055 high-quality cells from clinical specimens of 4 malignant and 4 non-malignant patients were investigated. Results We identified six common expression programs and six subtype-specific expression programs form malignant epithelial cells. The expression program of malignant epithelial cells exhibited activated EMT (Epithelial Mesenchymal Transition) in TME, which might indicate EMT intervention have a general therapeutic effect on various subtypes. Gene set enrichment analysis (GSEA) based on the top 50 highly NMF (non-negative matrix factorization) score genes in each program depicted the distinct function of each program in breast cancer progression. Moreover, we revealed the profound cellular heterogeneity of myeloid cell lineages in breast cancer. In macrophages, two mainly tumor associated macrophages (TAMs), TAM1 and TAM2, were also detected and the highly variable genes in TAM2 were strongly enriched in IFN-α and IFN-γ. The changes of lipid metabolism pathways in macrophages are closely related to the microenvironment of breast cancer. Conclusion We constructed a comprehensive single-cell transcriptome atlas of 54,055 cells from 4 malignant and 4 nonmalignant patients, providing insights into the mechanisms underlying breast cancer progression and the development of potential therapeutic strategies in breast cancer. |
| format | Article |
| id | doaj-art-a1c1cc4faeb14b62bc8e899678008986 |
| institution | Kabale University |
| issn | 1432-1335 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Cancer Research and Clinical Oncology |
| spelling | doaj-art-a1c1cc4faeb14b62bc8e8996780089862025-02-09T12:10:19ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352024-12-01151111410.1007/s00432-024-06015-7Single-cell transcriptomes of dissecting the intra-tumoral heterogeneity of breast cancer microenvironmentPeixian Chen0Kaifeng Liang1Xiaofan Mao2Qiuyuan Wu3Zhiyan Chen4Yabin Jin5Kairong Lin6Tiancheng He7Shuqing Yang8Huiqi Huang9Guolin Ye10Juntao Gao11Dan Zhou12Zhihao Zeng13Department of Breast Surgery, The First People’s Hospital of FoshanDepartment of Breast Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan)Clinical Research Institute, The First People’s Hospital of FoshanDepartment of Breast Surgery, The First People’s Hospital of FoshanDepartment of Breast Surgery, The First People’s Hospital of FoshanClinical Research Institute, The First People’s Hospital of FoshanClinical Research Institute, The First People’s Hospital of FoshanDepartment of Breast Surgery, The First People’s Hospital of FoshanDepartment of Breast Surgery, The First People’s Hospital of FoshanDepartment of Breast Surgery, The First People’s Hospital of FoshanDepartment of Breast Surgery, The First People’s Hospital of FoshanMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Tsinghua UniversityDepartment of Breast Surgery, The First People’s Hospital of FoshanDepartment of Breast Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan)Abstract Objective To investigate the mechanism by which heterogeneity in breast cancer developed and acted in single-cell transcriptomes. Methods The composition of breast cancer based on the single-cell transcriptomes of 54,055 high-quality cells from clinical specimens of 4 malignant and 4 non-malignant patients were investigated. Results We identified six common expression programs and six subtype-specific expression programs form malignant epithelial cells. The expression program of malignant epithelial cells exhibited activated EMT (Epithelial Mesenchymal Transition) in TME, which might indicate EMT intervention have a general therapeutic effect on various subtypes. Gene set enrichment analysis (GSEA) based on the top 50 highly NMF (non-negative matrix factorization) score genes in each program depicted the distinct function of each program in breast cancer progression. Moreover, we revealed the profound cellular heterogeneity of myeloid cell lineages in breast cancer. In macrophages, two mainly tumor associated macrophages (TAMs), TAM1 and TAM2, were also detected and the highly variable genes in TAM2 were strongly enriched in IFN-α and IFN-γ. The changes of lipid metabolism pathways in macrophages are closely related to the microenvironment of breast cancer. Conclusion We constructed a comprehensive single-cell transcriptome atlas of 54,055 cells from 4 malignant and 4 nonmalignant patients, providing insights into the mechanisms underlying breast cancer progression and the development of potential therapeutic strategies in breast cancer.https://doi.org/10.1007/s00432-024-06015-7Breast cancerTumor heterogeneitySingle-cell RNA-SeqEMTTumor associated macrophages (TAM) |
| spellingShingle | Peixian Chen Kaifeng Liang Xiaofan Mao Qiuyuan Wu Zhiyan Chen Yabin Jin Kairong Lin Tiancheng He Shuqing Yang Huiqi Huang Guolin Ye Juntao Gao Dan Zhou Zhihao Zeng Single-cell transcriptomes of dissecting the intra-tumoral heterogeneity of breast cancer microenvironment Journal of Cancer Research and Clinical Oncology Breast cancer Tumor heterogeneity Single-cell RNA-Seq EMT Tumor associated macrophages (TAM) |
| title | Single-cell transcriptomes of dissecting the intra-tumoral heterogeneity of breast cancer microenvironment |
| title_full | Single-cell transcriptomes of dissecting the intra-tumoral heterogeneity of breast cancer microenvironment |
| title_fullStr | Single-cell transcriptomes of dissecting the intra-tumoral heterogeneity of breast cancer microenvironment |
| title_full_unstemmed | Single-cell transcriptomes of dissecting the intra-tumoral heterogeneity of breast cancer microenvironment |
| title_short | Single-cell transcriptomes of dissecting the intra-tumoral heterogeneity of breast cancer microenvironment |
| title_sort | single cell transcriptomes of dissecting the intra tumoral heterogeneity of breast cancer microenvironment |
| topic | Breast cancer Tumor heterogeneity Single-cell RNA-Seq EMT Tumor associated macrophages (TAM) |
| url | https://doi.org/10.1007/s00432-024-06015-7 |
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