Therapeutic implications and comprehensive insights into cellular senescence and aging in the tumor microenvironment of sarcoma
Abstract Sarcoma (SARC), a diverse group of stromal tumors arising from mesenchymal tissues, is often associated with a poor prognosis. Emerging evidence indicates that senescent cells within the tumor microenvironment (TME) significantly contribute to cancer progression and metastasis. Although the...
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| Format: | Article |
| Language: | English |
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Springer
2025-01-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-01757-3 |
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| author | Pengfei Zan Yi Zhang Yidong Zhu Qingjing Chen Zhengwei Duan Yonghao Guan Kaiyuan Liu Anquan Shang Zihua Li |
| author_facet | Pengfei Zan Yi Zhang Yidong Zhu Qingjing Chen Zhengwei Duan Yonghao Guan Kaiyuan Liu Anquan Shang Zihua Li |
| author_sort | Pengfei Zan |
| collection | DOAJ |
| description | Abstract Sarcoma (SARC), a diverse group of stromal tumors arising from mesenchymal tissues, is often associated with a poor prognosis. Emerging evidence indicates that senescent cells within the tumor microenvironment (TME) significantly contribute to cancer progression and metastasis. Although the influence of senescence on SARC has been partially acknowledged, it has yet to be fully elucidated. In this study, we revealed that senescence level and age were associated with TME, immune treatment indicators, and prognosis in SARC. Utilizing the weighted gene co-expression network analysis and least absolute shrinkage and selection operator algorithm, we identified senescence-related genes and developed a senescence predictor. Three genes, RAD54, PIK3IP1, and TRIP13, were selected to construct a multiple linear regression model. Validation cohorts, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction confirmed that the predictor derived from these three genes possessed prognostic and pathological relevance. Our senescence predictor provides comprehensive insights into the molecular mechanisms of SARC and identifies potential biomarkers for prognosis, paving the way for effective treatments. The results of this study hold promise for developing therapeutic strategies tailored to the unique characteristics of SARC. |
| format | Article |
| id | doaj-art-f95725302eb5411696c7b3c28c2549a1 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-f95725302eb5411696c7b3c28c2549a12025-01-19T12:29:16ZengSpringerDiscover Oncology2730-60112025-01-0116111510.1007/s12672-025-01757-3Therapeutic implications and comprehensive insights into cellular senescence and aging in the tumor microenvironment of sarcomaPengfei Zan0Yi Zhang1Yidong Zhu2Qingjing Chen3Zhengwei Duan4Yonghao Guan5Kaiyuan Liu6Anquan Shang7Zihua Li8Department of Orthopedics, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Orthopedics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji UniversityDepartment of Traditional Chinese Medicine, Shanghai Tenth People’s Hospital, School of Medicine, Tongji UniversityDepartment of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Southern Medical UniversityDepartment of Orthopedics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji UniversityDepartment of Orthopedics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji UniversityDepartment of Orthopedics, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Laboratory Medicine, The Second People’s Hospital of Lianyungang, Bengbu Medical CollegeDepartment of Orthopedics, Shanghai Tenth People’s Hospital, School of Medicine, Tongji UniversityAbstract Sarcoma (SARC), a diverse group of stromal tumors arising from mesenchymal tissues, is often associated with a poor prognosis. Emerging evidence indicates that senescent cells within the tumor microenvironment (TME) significantly contribute to cancer progression and metastasis. Although the influence of senescence on SARC has been partially acknowledged, it has yet to be fully elucidated. In this study, we revealed that senescence level and age were associated with TME, immune treatment indicators, and prognosis in SARC. Utilizing the weighted gene co-expression network analysis and least absolute shrinkage and selection operator algorithm, we identified senescence-related genes and developed a senescence predictor. Three genes, RAD54, PIK3IP1, and TRIP13, were selected to construct a multiple linear regression model. Validation cohorts, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction confirmed that the predictor derived from these three genes possessed prognostic and pathological relevance. Our senescence predictor provides comprehensive insights into the molecular mechanisms of SARC and identifies potential biomarkers for prognosis, paving the way for effective treatments. The results of this study hold promise for developing therapeutic strategies tailored to the unique characteristics of SARC.https://doi.org/10.1007/s12672-025-01757-3SarcomaCellular senescenceAgingTumor microenvironment |
| spellingShingle | Pengfei Zan Yi Zhang Yidong Zhu Qingjing Chen Zhengwei Duan Yonghao Guan Kaiyuan Liu Anquan Shang Zihua Li Therapeutic implications and comprehensive insights into cellular senescence and aging in the tumor microenvironment of sarcoma Discover Oncology Sarcoma Cellular senescence Aging Tumor microenvironment |
| title | Therapeutic implications and comprehensive insights into cellular senescence and aging in the tumor microenvironment of sarcoma |
| title_full | Therapeutic implications and comprehensive insights into cellular senescence and aging in the tumor microenvironment of sarcoma |
| title_fullStr | Therapeutic implications and comprehensive insights into cellular senescence and aging in the tumor microenvironment of sarcoma |
| title_full_unstemmed | Therapeutic implications and comprehensive insights into cellular senescence and aging in the tumor microenvironment of sarcoma |
| title_short | Therapeutic implications and comprehensive insights into cellular senescence and aging in the tumor microenvironment of sarcoma |
| title_sort | therapeutic implications and comprehensive insights into cellular senescence and aging in the tumor microenvironment of sarcoma |
| topic | Sarcoma Cellular senescence Aging Tumor microenvironment |
| url | https://doi.org/10.1007/s12672-025-01757-3 |
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