Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution
Abstract Ovarian clear cell carcinoma (OCCC) represents a rare and aggressive subtype of epithelial ovarian cancer with distinctive clinical and molecular characteristics. However, the identification, origin, and molecular features of the malignant epithelial cells in OCCC remain poorly studied. We...
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| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08617-4 |
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| author | Qinhao Guo Xia Chen Rui Bi Haiming Li Meng Liu Xingzhu Ju Zheng Feng Jun Zhu Yizhen Li Xin Wang Qiuru Huang Jiaxin Li Xiaonan Zhou Ying Zheng Bo Zheng Xiaohua Wu Jun Yu Hao Wen |
| author_facet | Qinhao Guo Xia Chen Rui Bi Haiming Li Meng Liu Xingzhu Ju Zheng Feng Jun Zhu Yizhen Li Xin Wang Qiuru Huang Jiaxin Li Xiaonan Zhou Ying Zheng Bo Zheng Xiaohua Wu Jun Yu Hao Wen |
| author_sort | Qinhao Guo |
| collection | DOAJ |
| description | Abstract Ovarian clear cell carcinoma (OCCC) represents a rare and aggressive subtype of epithelial ovarian cancer with distinctive clinical and molecular characteristics. However, the identification, origin, and molecular features of the malignant epithelial cells in OCCC remain poorly studied. We establish an OCCC-associated transcriptional landscape using single-cell RNA sequencing and investigated the properties of epithelial cells in tissues from normal ovaries, ovarian endometriosis, primary OCCC and recurrent OCCC to assess the status of malignant epithelial cells. We identify a specific subcluster of malignant epithelial cells and further analyze them to discover 173 candidate factors associated with OCCC. Regulon and pseudotime trajectory analyses reveal six transcription factors (TFs) and their corresponding targets among these candidate factors, highlighting their roles in OCCC onset and reoccurrence. Through experimental validation, we confirm the crucial involvement of STAT3, KLF5, and TRIM28 in the proliferation and migration of OVISE cells. Silencing these three TFs also results in the down-regulation of their associated TF targets linked to OCCC. Overall, we characterize complex malignant-like cell populations at single-cell resolution and highlighted several TFs and their targets, providing essential resources for understanding the regulatory mechanisms underlying OCCC initiation and recurrence. |
| format | Article |
| id | doaj-art-8c6228fd4f654215842f290a9dd4cbca |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-8c6228fd4f654215842f290a9dd4cbca2025-08-20T03:46:24ZengNature PortfolioCommunications Biology2399-36422025-08-018111610.1038/s42003-025-08617-4Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolutionQinhao Guo0Xia Chen1Rui Bi2Haiming Li3Meng Liu4Xingzhu Ju5Zheng Feng6Jun Zhu7Yizhen Li8Xin Wang9Qiuru Huang10Jiaxin Li11Xiaonan Zhou12Ying Zheng13Bo Zheng14Xiaohua Wu15Jun Yu16Hao Wen17Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan UniversityInstitute of Reproductive Medicine, Jiangsu Province Key Laboratory in University for Inflammation and Molecular Drug Target, School of Medicine, Nantong UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical UniversityDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityInstitute of Reproductive Medicine, Jiangsu Province Key Laboratory in University for Inflammation and Molecular Drug Target, School of Medicine, Nantong UniversityInstitute of Reproductive Medicine, Jiangsu Province Key Laboratory in University for Inflammation and Molecular Drug Target, School of Medicine, Nantong UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Histology and Embryology, School of Medicine, Yangzhou UniversityState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical UniversityDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan UniversityInstitute of Reproductive Medicine, Jiangsu Province Key Laboratory in University for Inflammation and Molecular Drug Target, School of Medicine, Nantong UniversityDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan UniversityAbstract Ovarian clear cell carcinoma (OCCC) represents a rare and aggressive subtype of epithelial ovarian cancer with distinctive clinical and molecular characteristics. However, the identification, origin, and molecular features of the malignant epithelial cells in OCCC remain poorly studied. We establish an OCCC-associated transcriptional landscape using single-cell RNA sequencing and investigated the properties of epithelial cells in tissues from normal ovaries, ovarian endometriosis, primary OCCC and recurrent OCCC to assess the status of malignant epithelial cells. We identify a specific subcluster of malignant epithelial cells and further analyze them to discover 173 candidate factors associated with OCCC. Regulon and pseudotime trajectory analyses reveal six transcription factors (TFs) and their corresponding targets among these candidate factors, highlighting their roles in OCCC onset and reoccurrence. Through experimental validation, we confirm the crucial involvement of STAT3, KLF5, and TRIM28 in the proliferation and migration of OVISE cells. Silencing these three TFs also results in the down-regulation of their associated TF targets linked to OCCC. Overall, we characterize complex malignant-like cell populations at single-cell resolution and highlighted several TFs and their targets, providing essential resources for understanding the regulatory mechanisms underlying OCCC initiation and recurrence.https://doi.org/10.1038/s42003-025-08617-4 |
| spellingShingle | Qinhao Guo Xia Chen Rui Bi Haiming Li Meng Liu Xingzhu Ju Zheng Feng Jun Zhu Yizhen Li Xin Wang Qiuru Huang Jiaxin Li Xiaonan Zhou Ying Zheng Bo Zheng Xiaohua Wu Jun Yu Hao Wen Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution Communications Biology |
| title | Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution |
| title_full | Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution |
| title_fullStr | Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution |
| title_full_unstemmed | Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution |
| title_short | Epithelial characteristics of ovarian clear cell carcinoma at single-cell resolution |
| title_sort | epithelial characteristics of ovarian clear cell carcinoma at single cell resolution |
| url | https://doi.org/10.1038/s42003-025-08617-4 |
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