Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases
Abstract Leptomeningeal metastases (LM) occur in patients with breast cancer (BC) and lung cancer (LC) showing exceptionally poor prognosis. The cerebrospinal fluid (CSF) tumour microenvironment (TME) of LM patients is not well defined at a single‐cell level. Based on the 10× genomics single‐cell RN...
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| Format: | Article |
| Language: | English |
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Wiley
2022-06-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.885 |
| _version_ | 1828803449941131264 |
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| author | Haoyu Ruan Zhe Wang Ziwei Sun Jia Wei Lei Zhang Huanyu Ju Ting Wang Chao Zhang Ming Guan Shiyang Pan |
| author_facet | Haoyu Ruan Zhe Wang Ziwei Sun Jia Wei Lei Zhang Huanyu Ju Ting Wang Chao Zhang Ming Guan Shiyang Pan |
| author_sort | Haoyu Ruan |
| collection | DOAJ |
| description | Abstract Leptomeningeal metastases (LM) occur in patients with breast cancer (BC) and lung cancer (LC) showing exceptionally poor prognosis. The cerebrospinal fluid (CSF) tumour microenvironment (TME) of LM patients is not well defined at a single‐cell level. Based on the 10× genomics single‐cell RNA sequencing (scRNA‐seq) data from GEO database including five patient‐derived CSF samples of BC‐LM and LC‐LM, and four patient‐derived CSF samples of idiopathic intracranial hypertension (IIH) as controls, we analysed single‐cell transcriptome characteristics of CSF TME in LM patients compared to controls simultaneously and comprehensively. In addition, we performed 10× genomics scRNA‐seq on CSF cells derived from a BC‐LM patient to help generate a solid conclusion. The CSF macrophages in LM patients showing M2‐subtype signature and the emergence of regulatory T cells in LM confirmed the direction of tumour immunity toward immunosuppression. Then, the characteristics of CSF circulating tumour cells (CTCs) of breast cancer LM (BC‐LM) patients were classified into five molecular subtypes by PAM50 model. The communication between macrophages and five subtype‐specific CSF‐CTCs showed largest number of ligand‐receptor interactions. The five subtypes‐specific CSF‐CTCs showed great heterogeneities which were manifested in cell proliferation and cancer‐testis antigens expression. Gene regulatory networks (GRNs) analysis revealed that transcription factor SREBF2 was universally activated in the five subtypes‐specific CSF‐CTCs. Our results will provide inspiration on new directions of the mechanism research, diagnosis and therapy of LM. |
| first_indexed | 2024-12-12T07:23:48Z |
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| id | doaj.art-8a971b0e671c4009adb53b894a309718 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-12-12T07:23:48Z |
| publishDate | 2022-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-8a971b0e671c4009adb53b894a3097182022-12-22T00:33:14ZengWileyClinical and Translational Medicine2001-13262022-06-01126n/an/a10.1002/ctm2.885Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastasesHaoyu Ruan0Zhe Wang1Ziwei Sun2Jia Wei3Lei Zhang4Huanyu Ju5Ting Wang6Chao Zhang7Ming Guan8Shiyang Pan9Department of Laboratory Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Physiology, Second Military Medical University Shanghai ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaDepartment of Plastic and Reconstructive Surgery Shanghai Institute of Precision Medicine Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Laboratory Medicine Huashan Hospital Fudan University Shanghai ChinaDepartment of Laboratory Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing ChinaAbstract Leptomeningeal metastases (LM) occur in patients with breast cancer (BC) and lung cancer (LC) showing exceptionally poor prognosis. The cerebrospinal fluid (CSF) tumour microenvironment (TME) of LM patients is not well defined at a single‐cell level. Based on the 10× genomics single‐cell RNA sequencing (scRNA‐seq) data from GEO database including five patient‐derived CSF samples of BC‐LM and LC‐LM, and four patient‐derived CSF samples of idiopathic intracranial hypertension (IIH) as controls, we analysed single‐cell transcriptome characteristics of CSF TME in LM patients compared to controls simultaneously and comprehensively. In addition, we performed 10× genomics scRNA‐seq on CSF cells derived from a BC‐LM patient to help generate a solid conclusion. The CSF macrophages in LM patients showing M2‐subtype signature and the emergence of regulatory T cells in LM confirmed the direction of tumour immunity toward immunosuppression. Then, the characteristics of CSF circulating tumour cells (CTCs) of breast cancer LM (BC‐LM) patients were classified into five molecular subtypes by PAM50 model. The communication between macrophages and five subtype‐specific CSF‐CTCs showed largest number of ligand‐receptor interactions. The five subtypes‐specific CSF‐CTCs showed great heterogeneities which were manifested in cell proliferation and cancer‐testis antigens expression. Gene regulatory networks (GRNs) analysis revealed that transcription factor SREBF2 was universally activated in the five subtypes‐specific CSF‐CTCs. Our results will provide inspiration on new directions of the mechanism research, diagnosis and therapy of LM.https://doi.org/10.1002/ctm2.885Cerebrospinal fluidcirculating tumour cellsgene regulatory networksleptomeningeal metastasestumour microenvironment |
| spellingShingle | Haoyu Ruan Zhe Wang Ziwei Sun Jia Wei Lei Zhang Huanyu Ju Ting Wang Chao Zhang Ming Guan Shiyang Pan Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases Clinical and Translational Medicine Cerebrospinal fluid circulating tumour cells gene regulatory networks leptomeningeal metastases tumour microenvironment |
| title | Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases |
| title_full | Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases |
| title_fullStr | Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases |
| title_full_unstemmed | Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases |
| title_short | Single‐cell RNA sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases |
| title_sort | single cell rna sequencing reveals the characteristics of cerebrospinal fluid tumour environment in breast cancer and lung cancer leptomeningeal metastases |
| topic | Cerebrospinal fluid circulating tumour cells gene regulatory networks leptomeningeal metastases tumour microenvironment |
| url | https://doi.org/10.1002/ctm2.885 |
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