Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: Implications for prognosis and immunotherapy
Background: Prostate cancer stands as the second most common malignancy among men, notorious for its intricate heterogeneity, especially evident in metastatic disease. This complexity presents substantial challenges in treatment efficacy and patient prognosis. Objective: This study endeavors to eluc...
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| Format: | Article |
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Elsevier
2025-02-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324003814 |
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| author | Chen Ding Jiange Wang Jie Wang Jiqiang Niu Zhikai Xiahou Zhou Sun Zhenzhen Zhao Dongyang Zeng |
| author_facet | Chen Ding Jiange Wang Jie Wang Jiqiang Niu Zhikai Xiahou Zhou Sun Zhenzhen Zhao Dongyang Zeng |
| author_sort | Chen Ding |
| collection | DOAJ |
| description | Background: Prostate cancer stands as the second most common malignancy among men, notorious for its intricate heterogeneity, especially evident in metastatic disease. This complexity presents substantial challenges in treatment efficacy and patient prognosis. Objective: This study endeavors to elucidate the multifaceted roles of cancer-associated fibroblasts within the tumor microenvironment of prostate cancer, with a focus on their implications for disease prognosis and the potential for novel immunotherapeutic strategies. Methods: Leveraging advanced single-cell RNA sequencing technology, we meticulously characterized the diverse CAF subpopulations within prostate cancer samples. Our analysis identified four predominant subsets: C0 IER2+, C1 ABCA8+, C2 ABI3BP+, and C3 MEOX2+. We conducted comprehensive gene expression profiling to construct a robust prognostic model reflecting the clinical relevance of these subpopulations. Results: C1 ABCA8+ fibroblasts demonstrated heightened proliferative activity, underscoring their pivotal role in fostering tumor growth and metastasis via intricate signaling pathways. In vitro experiments verified that the T transcription factor NFAT5 of C1 ABCA8+ fibroblasts subpopulation was knocked down in LNCaP clone FGC and 22Rv1 cell lines, which was closely related to the proliferation of PC. Moreover, we identified key genes linked to patient outcomes and immune landscape alterations, reinforcing the prognostic significance of CAF characteristics in this context. Conclusion: This investigation illuminates the critical potential of targeting CAFs to augment immunotherapeutic approaches in prostate cancer. Our findings contribute to a deeper understanding of the TME's complexity, advocating for further exploration into CAF-targeted therapies aimed at enhancing treatment responses and ultimately improving patient outcomes. |
| format | Article |
| id | doaj-art-7df5b72c4c9d4c729cbdd0579bc173d6 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-7df5b72c4c9d4c729cbdd0579bc173d62025-01-22T05:41:30ZengElsevierTranslational Oncology1936-52332025-02-0152102255Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: Implications for prognosis and immunotherapyChen Ding0Jiange Wang1Jie Wang2Jiqiang Niu3Zhikai Xiahou4Zhou Sun5Zhenzhen Zhao6Dongyang Zeng7Department of Urology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, 136 Jingzhou Street, Xiangyang, Hubei 441021, PR ChinaDepartment of Urology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, 136 Jingzhou Street, Xiangyang, Hubei 441021, PR ChinaDepartment of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130000, China; Department of Urology, The Second People's Hospital of Meishan City, Meishan, Sichuan, ChinaDepartment of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130000, ChinaChina Institute of Sport and Health Science, Beijing Sport University, Beijing, ChinaDepartment of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130000, China; Corresponding authors.The first clinical medical college of Shandong university of Traditional Chinese Medicine, Jinan 250014, China; Corresponding authors.Department of Urology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, 136 Jingzhou Street, Xiangyang, Hubei 441021, PR China; Corresponding authors.Background: Prostate cancer stands as the second most common malignancy among men, notorious for its intricate heterogeneity, especially evident in metastatic disease. This complexity presents substantial challenges in treatment efficacy and patient prognosis. Objective: This study endeavors to elucidate the multifaceted roles of cancer-associated fibroblasts within the tumor microenvironment of prostate cancer, with a focus on their implications for disease prognosis and the potential for novel immunotherapeutic strategies. Methods: Leveraging advanced single-cell RNA sequencing technology, we meticulously characterized the diverse CAF subpopulations within prostate cancer samples. Our analysis identified four predominant subsets: C0 IER2+, C1 ABCA8+, C2 ABI3BP+, and C3 MEOX2+. We conducted comprehensive gene expression profiling to construct a robust prognostic model reflecting the clinical relevance of these subpopulations. Results: C1 ABCA8+ fibroblasts demonstrated heightened proliferative activity, underscoring their pivotal role in fostering tumor growth and metastasis via intricate signaling pathways. In vitro experiments verified that the T transcription factor NFAT5 of C1 ABCA8+ fibroblasts subpopulation was knocked down in LNCaP clone FGC and 22Rv1 cell lines, which was closely related to the proliferation of PC. Moreover, we identified key genes linked to patient outcomes and immune landscape alterations, reinforcing the prognostic significance of CAF characteristics in this context. Conclusion: This investigation illuminates the critical potential of targeting CAFs to augment immunotherapeutic approaches in prostate cancer. Our findings contribute to a deeper understanding of the TME's complexity, advocating for further exploration into CAF-targeted therapies aimed at enhancing treatment responses and ultimately improving patient outcomes.http://www.sciencedirect.com/science/article/pii/S1936523324003814Single cell RNA sequencingProstate cancerCancer-associated fibroblastsrisk scorePrognosis |
| spellingShingle | Chen Ding Jiange Wang Jie Wang Jiqiang Niu Zhikai Xiahou Zhou Sun Zhenzhen Zhao Dongyang Zeng Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: Implications for prognosis and immunotherapy Translational Oncology Single cell RNA sequencing Prostate cancer Cancer-associated fibroblasts risk score Prognosis |
| title | Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: Implications for prognosis and immunotherapy |
| title_full | Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: Implications for prognosis and immunotherapy |
| title_fullStr | Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: Implications for prognosis and immunotherapy |
| title_full_unstemmed | Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: Implications for prognosis and immunotherapy |
| title_short | Heterogeneity of cancer-associated fibroblast subpopulations in prostate cancer: Implications for prognosis and immunotherapy |
| title_sort | heterogeneity of cancer associated fibroblast subpopulations in prostate cancer implications for prognosis and immunotherapy |
| topic | Single cell RNA sequencing Prostate cancer Cancer-associated fibroblasts risk score Prognosis |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324003814 |
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