Revealing the role of cancer-associated fibroblast senescence in prognosis and immune landscape in pancreatic cancer
Summary: Cancer-associated fibroblasts (CAFs) represent a major contributor to tumor growth. Cellular senescence is a state of cell-cycle arrest characterized by a pro-inflammatory phenotype. The potential impact of CAF senescence on tumor progression and the tumor microenvironment (TME) remains to...
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Elsevier
2025-01-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224028396 |
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| author | Luyao Liu Hai Huang Bin Cheng Huaping Xie Wang Peng Haochen Cui Jingwen Liang Mengdie Cao Yilei Yang Wei Chen Ronghua Wang Yuchong Zhao |
| author_facet | Luyao Liu Hai Huang Bin Cheng Huaping Xie Wang Peng Haochen Cui Jingwen Liang Mengdie Cao Yilei Yang Wei Chen Ronghua Wang Yuchong Zhao |
| author_sort | Luyao Liu |
| collection | DOAJ |
| description | Summary: Cancer-associated fibroblasts (CAFs) represent a major contributor to tumor growth. Cellular senescence is a state of cell-cycle arrest characterized by a pro-inflammatory phenotype. The potential impact of CAF senescence on tumor progression and the tumor microenvironment (TME) remains to be elucidated. Here, we systematically investigated the relationship between CAF senescence and the TME of pancreatic ductal adenocarcinoma (PDAC) based on multi-omics analysis and functional experiments. CAF senescence promotes tumor progression in vitro and in vivo and contributes to the formation of immunosuppressive TME. A CAF-senescence-related risk score was developed to predict overall survival, immune landscape, and treatment sensitivity in patients with PDAC. Further experiments revealed that plasminogen activator urokinase (PLAU) derived from senescent CAFs (SCAFs) promoted PDAC progression and was involved in immunosuppression. Together, these findings suggested that CAF senescence was correlated with tumor progression, and the CAF-senescence-based machine learning model could potentially predict prognosis in patients with PDAC. |
| format | Article |
| id | doaj-art-c54ab2eb9ce24903a759b45d4e822d1d |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-c54ab2eb9ce24903a759b45d4e822d1d2025-08-20T02:39:48ZengElsevieriScience2589-00422025-01-0128111161210.1016/j.isci.2024.111612Revealing the role of cancer-associated fibroblast senescence in prognosis and immune landscape in pancreatic cancerLuyao Liu0Hai Huang1Bin Cheng2Huaping Xie3Wang Peng4Haochen Cui5Jingwen Liang6Mengdie Cao7Yilei Yang8Wei Chen9Ronghua Wang10Yuchong Zhao11Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Corresponding authorDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USADepartment of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Corresponding authorSummary: Cancer-associated fibroblasts (CAFs) represent a major contributor to tumor growth. Cellular senescence is a state of cell-cycle arrest characterized by a pro-inflammatory phenotype. The potential impact of CAF senescence on tumor progression and the tumor microenvironment (TME) remains to be elucidated. Here, we systematically investigated the relationship between CAF senescence and the TME of pancreatic ductal adenocarcinoma (PDAC) based on multi-omics analysis and functional experiments. CAF senescence promotes tumor progression in vitro and in vivo and contributes to the formation of immunosuppressive TME. A CAF-senescence-related risk score was developed to predict overall survival, immune landscape, and treatment sensitivity in patients with PDAC. Further experiments revealed that plasminogen activator urokinase (PLAU) derived from senescent CAFs (SCAFs) promoted PDAC progression and was involved in immunosuppression. Together, these findings suggested that CAF senescence was correlated with tumor progression, and the CAF-senescence-based machine learning model could potentially predict prognosis in patients with PDAC.http://www.sciencedirect.com/science/article/pii/S2589004224028396MicroenvironmentImmune responseCancer |
| spellingShingle | Luyao Liu Hai Huang Bin Cheng Huaping Xie Wang Peng Haochen Cui Jingwen Liang Mengdie Cao Yilei Yang Wei Chen Ronghua Wang Yuchong Zhao Revealing the role of cancer-associated fibroblast senescence in prognosis and immune landscape in pancreatic cancer iScience Microenvironment Immune response Cancer |
| title | Revealing the role of cancer-associated fibroblast senescence in prognosis and immune landscape in pancreatic cancer |
| title_full | Revealing the role of cancer-associated fibroblast senescence in prognosis and immune landscape in pancreatic cancer |
| title_fullStr | Revealing the role of cancer-associated fibroblast senescence in prognosis and immune landscape in pancreatic cancer |
| title_full_unstemmed | Revealing the role of cancer-associated fibroblast senescence in prognosis and immune landscape in pancreatic cancer |
| title_short | Revealing the role of cancer-associated fibroblast senescence in prognosis and immune landscape in pancreatic cancer |
| title_sort | revealing the role of cancer associated fibroblast senescence in prognosis and immune landscape in pancreatic cancer |
| topic | Microenvironment Immune response Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224028396 |
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