Stemness-driven clusters in ovarian cancer: immune characteristics and prognostic implications
BackgroundOvarian cancer (OC) is the most common malignant gynecological tumor. Cancer cells with high stemness often exhibit resistance to anti-tumor therapies, contributing to recurrence and poor prognosis. However, stemness-related subtypes in OC and their therapeutic implications remain underexp...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1577283/full |
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| author | Xinyan Zeng Xinyan Zeng Wentian Wu Xiaoqin Li Xiaoqin Li Xiaorui Wu Xiaorui Wu Yingying Du Ping Li Ping Li Ping Li |
| author_facet | Xinyan Zeng Xinyan Zeng Wentian Wu Xiaoqin Li Xiaoqin Li Xiaorui Wu Xiaorui Wu Yingying Du Ping Li Ping Li Ping Li |
| author_sort | Xinyan Zeng |
| collection | DOAJ |
| description | BackgroundOvarian cancer (OC) is the most common malignant gynecological tumor. Cancer cells with high stemness often exhibit resistance to anti-tumor therapies, contributing to recurrence and poor prognosis. However, stemness-related subtypes in OC and their therapeutic implications remain underexplored.MethodsWe identified stemness-associated genes by comparing transcriptome profiles between adherent and sphere-forming SKOV3 cells. Unsupervised clustering was applied to define stemness-related molecular subgroups in OC patients. A prognostic model was constructed using WGCNA and LASSO regression, and a nomogram was developed by integrating clinicopathological variables. Differences in the tumor microenvironment (TME), tumor mutation burden (TMB), immune checkpoint expression, and drug sensitivities were evaluated between risk groups. Single-cell RNA sequencing was used to investigate stemness-related cell types. Functional assays were conducted to validate the role of AKAP12 in OC progression.ResultsThree distinct stemness-related subgroups were identified with significant differences in prognosis and immunological features. Fibroblasts were identified as major contributors to the maintenance of stemness traits in the TME. AKAP12 was found to be positively associated with stemness phenotypes. Knockdown of AKAP12 reduced tumor sphere formation, impaired cell migration, and enhanced cisplatin sensitivity. Immunohistochemistry in clinical samples and OC organoids confirmed the correlation between AKAP12 and the immune checkpoint molecule OX40L.ConclusionThis study establishes a novel stemness-related gene signature for prognosis prediction and therapeutic stratification in OC. AKAP12 was identified as a potential biomarker and therapeutic target, offering new avenues for precision treatment in stemness-driven OC. |
| format | Article |
| id | doaj-art-58e87d4e6e6c42f4a111b8c353fac649 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-58e87d4e6e6c42f4a111b8c353fac6492025-08-20T03:10:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15772831577283Stemness-driven clusters in ovarian cancer: immune characteristics and prognostic implicationsXinyan Zeng0Xinyan Zeng1Wentian Wu2Xiaoqin Li3Xiaoqin Li4Xiaorui Wu5Xiaorui Wu6Yingying Du7Ping Li8Ping Li9Ping Li10Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Anhui Medical University, Hefei, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Anhui Medical University, Hefei, ChinaDepartment of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Anhui Medical University, Hefei, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Anhui Medical University, Hefei, ChinaGraduate School of Anhui University of Traditional Chinese Medicine, Hefei, ChinaBackgroundOvarian cancer (OC) is the most common malignant gynecological tumor. Cancer cells with high stemness often exhibit resistance to anti-tumor therapies, contributing to recurrence and poor prognosis. However, stemness-related subtypes in OC and their therapeutic implications remain underexplored.MethodsWe identified stemness-associated genes by comparing transcriptome profiles between adherent and sphere-forming SKOV3 cells. Unsupervised clustering was applied to define stemness-related molecular subgroups in OC patients. A prognostic model was constructed using WGCNA and LASSO regression, and a nomogram was developed by integrating clinicopathological variables. Differences in the tumor microenvironment (TME), tumor mutation burden (TMB), immune checkpoint expression, and drug sensitivities were evaluated between risk groups. Single-cell RNA sequencing was used to investigate stemness-related cell types. Functional assays were conducted to validate the role of AKAP12 in OC progression.ResultsThree distinct stemness-related subgroups were identified with significant differences in prognosis and immunological features. Fibroblasts were identified as major contributors to the maintenance of stemness traits in the TME. AKAP12 was found to be positively associated with stemness phenotypes. Knockdown of AKAP12 reduced tumor sphere formation, impaired cell migration, and enhanced cisplatin sensitivity. Immunohistochemistry in clinical samples and OC organoids confirmed the correlation between AKAP12 and the immune checkpoint molecule OX40L.ConclusionThis study establishes a novel stemness-related gene signature for prognosis prediction and therapeutic stratification in OC. AKAP12 was identified as a potential biomarker and therapeutic target, offering new avenues for precision treatment in stemness-driven OC.https://www.frontiersin.org/articles/10.3389/fonc.2025.1577283/fullovarian cancerstemnessimmune checkpointsdrug resistancetumor organoid |
| spellingShingle | Xinyan Zeng Xinyan Zeng Wentian Wu Xiaoqin Li Xiaoqin Li Xiaorui Wu Xiaorui Wu Yingying Du Ping Li Ping Li Ping Li Stemness-driven clusters in ovarian cancer: immune characteristics and prognostic implications Frontiers in Oncology ovarian cancer stemness immune checkpoints drug resistance tumor organoid |
| title | Stemness-driven clusters in ovarian cancer: immune characteristics and prognostic implications |
| title_full | Stemness-driven clusters in ovarian cancer: immune characteristics and prognostic implications |
| title_fullStr | Stemness-driven clusters in ovarian cancer: immune characteristics and prognostic implications |
| title_full_unstemmed | Stemness-driven clusters in ovarian cancer: immune characteristics and prognostic implications |
| title_short | Stemness-driven clusters in ovarian cancer: immune characteristics and prognostic implications |
| title_sort | stemness driven clusters in ovarian cancer immune characteristics and prognostic implications |
| topic | ovarian cancer stemness immune checkpoints drug resistance tumor organoid |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1577283/full |
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