Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases
Abstract Breast cancer is the most common malignant tumor in the world, and its metastasis is the main cause of death in breast cancer patients. However, the differences between primary breast cancer tissue and lymphatic node, bone, and brain metastases at the single-cell level are not fully underst...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-85531-z |
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| author | Longyu Zhu Miaomiao Liu Yuguang Shang Jingge Cheng Hongye Zhao Jun Zhang Dongxing Shen |
| author_facet | Longyu Zhu Miaomiao Liu Yuguang Shang Jingge Cheng Hongye Zhao Jun Zhang Dongxing Shen |
| author_sort | Longyu Zhu |
| collection | DOAJ |
| description | Abstract Breast cancer is the most common malignant tumor in the world, and its metastasis is the main cause of death in breast cancer patients. However, the differences between primary breast cancer tissue and lymphatic node, bone, and brain metastases at the single-cell level are not fully understood. We analyzed the microenvironment heterogeneity in samples of primary breast cancer (n = 4), breast cancer lymphatic node metastasis (n = 4), breast cancer brain metastasis (n = 3), and breast cancer bone metastasis (n = 2) using single-cell sequencing data from the GEO database. The malignant epithelial cells were characterized by InferCNV algorithm. The cell-cell communication was analyzed using CellChat package. The biological function of cell subpopulations was analyzed using gene set variation analysis. The expression of STMN1 was analyzed using immunohistochemical staining. The proportion of pCAFs in breast cancer was explored using multispectral immunohistochemical staining. We identified seven cell clusters in primary and metastatic breast cancer (Lymphatic node, brain, and bone metastases) by analyzing single-cell transcriptomic profiles. T-NK and B cells dominated breast cancer with lymphatic node metastasis, whereas fibroblasts were prevalent in brain metastases and primary breast cancer. We identified five T cells (T memory, CD8 + T cells, regulatory T cells, natural killer cells, CD4 + T cells), three B cells (naïve B cells, memory B cells, plasma B cells), and five cancer-associated fibroblasts (CAFs) subpopulations (Smooth muscle cells (SMC), pericyte, antigen-presenting CAFs (apCAFs), proliferative CAFs (pCAFs), and matrix CAFs (mCAFs)). Notably. pCAFs dominated breast cancer with lymphatic node, bone, and brain metastasis. Furthermore, we identified four malignant epithelial cell subpopulations: G0, G1, G2, and G3. The G2 cell population exhibited strong invasion ability, it can differentiate into G3 with strong proliferative ability and proliferation-related G1 cell population after metastasis. Cell-cell communication demonstrated an interaction between pCAFs and metastasis-associated malignant epithelial cells. Finally, we discovered that in advanced breast cancer, the proportion of pCAF increased and was associated with a poor prognosis of breast cancer. This study elucidated the potential cellular origins and drivers of breast cancer metastases to lymphatic nodes, brain, and bone, utilizing single-cell transcriptomic profiles. Furthermore, it demonstrated that increased pCAFs were associated with advanced breast cancer and a poor prognosis. |
| format | Article |
| id | doaj-art-15940d95475043c8bac7bb30f1a0e2ca |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-15940d95475043c8bac7bb30f1a0e2ca2025-01-19T12:23:34ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-85531-zSingle-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastasesLongyu Zhu0Miaomiao Liu1Yuguang Shang2Jingge Cheng3Hongye Zhao4Jun Zhang5Dongxing Shen6Department of Radiotherapy Oncology, The Fourth Hospital of Hebei Medical UniversityThe Fifth Department of Oncology, Hebei General HospitalDepartment of Radiotherapy Oncology, The Fourth Hospital of Hebei Medical UniversityDepartment of Thoracic Surgery, The Fourth Hospital of Hebei Medical UniversityDepartment of Dermatology, The Fourth Hospital of Hebei Medical UniversityDepartment of Radiotherapy Oncology, The Fourth Hospital of Hebei Medical UniversityDepartment of Radiotherapy Oncology, The Fourth Hospital of Hebei Medical UniversityAbstract Breast cancer is the most common malignant tumor in the world, and its metastasis is the main cause of death in breast cancer patients. However, the differences between primary breast cancer tissue and lymphatic node, bone, and brain metastases at the single-cell level are not fully understood. We analyzed the microenvironment heterogeneity in samples of primary breast cancer (n = 4), breast cancer lymphatic node metastasis (n = 4), breast cancer brain metastasis (n = 3), and breast cancer bone metastasis (n = 2) using single-cell sequencing data from the GEO database. The malignant epithelial cells were characterized by InferCNV algorithm. The cell-cell communication was analyzed using CellChat package. The biological function of cell subpopulations was analyzed using gene set variation analysis. The expression of STMN1 was analyzed using immunohistochemical staining. The proportion of pCAFs in breast cancer was explored using multispectral immunohistochemical staining. We identified seven cell clusters in primary and metastatic breast cancer (Lymphatic node, brain, and bone metastases) by analyzing single-cell transcriptomic profiles. T-NK and B cells dominated breast cancer with lymphatic node metastasis, whereas fibroblasts were prevalent in brain metastases and primary breast cancer. We identified five T cells (T memory, CD8 + T cells, regulatory T cells, natural killer cells, CD4 + T cells), three B cells (naïve B cells, memory B cells, plasma B cells), and five cancer-associated fibroblasts (CAFs) subpopulations (Smooth muscle cells (SMC), pericyte, antigen-presenting CAFs (apCAFs), proliferative CAFs (pCAFs), and matrix CAFs (mCAFs)). Notably. pCAFs dominated breast cancer with lymphatic node, bone, and brain metastasis. Furthermore, we identified four malignant epithelial cell subpopulations: G0, G1, G2, and G3. The G2 cell population exhibited strong invasion ability, it can differentiate into G3 with strong proliferative ability and proliferation-related G1 cell population after metastasis. Cell-cell communication demonstrated an interaction between pCAFs and metastasis-associated malignant epithelial cells. Finally, we discovered that in advanced breast cancer, the proportion of pCAF increased and was associated with a poor prognosis of breast cancer. This study elucidated the potential cellular origins and drivers of breast cancer metastases to lymphatic nodes, brain, and bone, utilizing single-cell transcriptomic profiles. Furthermore, it demonstrated that increased pCAFs were associated with advanced breast cancer and a poor prognosis.https://doi.org/10.1038/s41598-025-85531-zBreast cancerDistinct metastasisMalignant epithelial cellspCAFsPrognosis |
| spellingShingle | Longyu Zhu Miaomiao Liu Yuguang Shang Jingge Cheng Hongye Zhao Jun Zhang Dongxing Shen Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases Scientific Reports Breast cancer Distinct metastasis Malignant epithelial cells pCAFs Prognosis |
| title | Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases |
| title_full | Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases |
| title_fullStr | Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases |
| title_full_unstemmed | Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases |
| title_short | Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases |
| title_sort | single cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node bone and brain metastases |
| topic | Breast cancer Distinct metastasis Malignant epithelial cells pCAFs Prognosis |
| url | https://doi.org/10.1038/s41598-025-85531-z |
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