A novel aging-associated lncRNA signature for predicting prognosis in osteosarcoma
Abstract Osteosarcoma (OS) is one of the most prevalent bone tumors in adolescents, and the correlation between aging and OS remains unclear. Currently, few accurate and reliable biomarkers have been determined for OS prognosis. To address this issue, we carried out a detailed bioinformatics analysi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-51732-1 |
| _version_ | 1797349925204262912 |
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| author | Yi He Xiao Huang Yajie Ma Guohui Yang Yuqing Cui Xuefeng Lv Rongling Zhao Huifang Jin Yalin Tong Xinyu Zhang Jitian Li Mengle Peng |
| author_facet | Yi He Xiao Huang Yajie Ma Guohui Yang Yuqing Cui Xuefeng Lv Rongling Zhao Huifang Jin Yalin Tong Xinyu Zhang Jitian Li Mengle Peng |
| author_sort | Yi He |
| collection | DOAJ |
| description | Abstract Osteosarcoma (OS) is one of the most prevalent bone tumors in adolescents, and the correlation between aging and OS remains unclear. Currently, few accurate and reliable biomarkers have been determined for OS prognosis. To address this issue, we carried out a detailed bioinformatics analysis based on OS with data from the Cancer Genome Atlas data portal and Human Aging Genomic Resources database, as well as in vitro experiments. A total of 88 OS samples with gene expression profiles and corresponding clinical characteristics were obtained. Through univariate Cox regression analysis and survival analysis, 10 aging-associated survival lncRNAs (AASRs) were identified to be associated with the overall survival of OS patients. Based on the expression levels of the 10 AASRs, the OS patients were classified into two clusters (Cluster A and Cluster B). Cluster A had a worse prognosis, while Cluster B had a better prognosis. Then, 5 AASRs were ultimately included in the signature through least absolute shrinkage and selection operator-Cox regression analysis. Kaplan‒Meier survival analysis verified that the high-risk group exhibited a worse prognosis than the low-risk group. Furthermore, univariate and multivariate Cox regression analyses confirmed that the riskScore was an independent prognostic factor for OS patients. Subsequently, we discovered that the risk signature was correlated with the properties of the tumor microenvironment and immune cell infiltration. Specifically, there was a positive association between the risk model and naïve B cells, resting dendritic cells and gamma delta T cells, while it was negatively related to CD8+ T cells. Finally, in vitro experiments, we found that UNC5B-AS1 inhibited OS cells from undergoing cellular senescence and apoptosis, thereby promoting OS cells proliferation. In conclusion, we constructed and verified a 5 AASR-based signature, that exhibited excellent performance in evaluating the overall survival of OS patients. In addition, we found that UNC5B-AS1 might inhibit the senescence process, thus leading to the development and progression of OS. Our findings may provide novel insights into the treatment of OS patients. |
| first_indexed | 2024-03-08T12:37:25Z |
| format | Article |
| id | doaj.art-595e8530ed9e40b89dfdc2d335d36434 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T12:37:25Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-595e8530ed9e40b89dfdc2d335d364342024-01-21T12:20:31ZengNature PortfolioScientific Reports2045-23222024-01-0114111410.1038/s41598-024-51732-1A novel aging-associated lncRNA signature for predicting prognosis in osteosarcomaYi He0Xiao Huang1Yajie Ma2Guohui Yang3Yuqing Cui4Xuefeng Lv5Rongling Zhao6Huifang Jin7Yalin Tong8Xinyu Zhang9Jitian Li10Mengle Peng11Department of Mini-Invasive Spinal Surgery, The Third People’s Hospital of Henan ProvinceDepartment of Clinical Laboratory, Luohe Central HospitalDepartment of Medical Affair, The Third People’s Hospital of Henan ProvinceDepartment of Emergency Surgery, The First Affiliated Hospital of Zhengzhou UniversityGeneral ICU, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou UniversityDepartment of Clinical Laboratory, The Third People’s Hospital of Henan ProvinceDepartment of Blood Transfusion, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Digestion, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Medical Affair, The Third People’s Hospital of Henan ProvinceHenan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Henan Provincial Orthopedic Institute, Henan University of Chinese MedicineDepartment of Clinical Laboratory, The Third People’s Hospital of Henan ProvinceAbstract Osteosarcoma (OS) is one of the most prevalent bone tumors in adolescents, and the correlation between aging and OS remains unclear. Currently, few accurate and reliable biomarkers have been determined for OS prognosis. To address this issue, we carried out a detailed bioinformatics analysis based on OS with data from the Cancer Genome Atlas data portal and Human Aging Genomic Resources database, as well as in vitro experiments. A total of 88 OS samples with gene expression profiles and corresponding clinical characteristics were obtained. Through univariate Cox regression analysis and survival analysis, 10 aging-associated survival lncRNAs (AASRs) were identified to be associated with the overall survival of OS patients. Based on the expression levels of the 10 AASRs, the OS patients were classified into two clusters (Cluster A and Cluster B). Cluster A had a worse prognosis, while Cluster B had a better prognosis. Then, 5 AASRs were ultimately included in the signature through least absolute shrinkage and selection operator-Cox regression analysis. Kaplan‒Meier survival analysis verified that the high-risk group exhibited a worse prognosis than the low-risk group. Furthermore, univariate and multivariate Cox regression analyses confirmed that the riskScore was an independent prognostic factor for OS patients. Subsequently, we discovered that the risk signature was correlated with the properties of the tumor microenvironment and immune cell infiltration. Specifically, there was a positive association between the risk model and naïve B cells, resting dendritic cells and gamma delta T cells, while it was negatively related to CD8+ T cells. Finally, in vitro experiments, we found that UNC5B-AS1 inhibited OS cells from undergoing cellular senescence and apoptosis, thereby promoting OS cells proliferation. In conclusion, we constructed and verified a 5 AASR-based signature, that exhibited excellent performance in evaluating the overall survival of OS patients. In addition, we found that UNC5B-AS1 might inhibit the senescence process, thus leading to the development and progression of OS. Our findings may provide novel insights into the treatment of OS patients.https://doi.org/10.1038/s41598-024-51732-1 |
| spellingShingle | Yi He Xiao Huang Yajie Ma Guohui Yang Yuqing Cui Xuefeng Lv Rongling Zhao Huifang Jin Yalin Tong Xinyu Zhang Jitian Li Mengle Peng A novel aging-associated lncRNA signature for predicting prognosis in osteosarcoma Scientific Reports |
| title | A novel aging-associated lncRNA signature for predicting prognosis in osteosarcoma |
| title_full | A novel aging-associated lncRNA signature for predicting prognosis in osteosarcoma |
| title_fullStr | A novel aging-associated lncRNA signature for predicting prognosis in osteosarcoma |
| title_full_unstemmed | A novel aging-associated lncRNA signature for predicting prognosis in osteosarcoma |
| title_short | A novel aging-associated lncRNA signature for predicting prognosis in osteosarcoma |
| title_sort | novel aging associated lncrna signature for predicting prognosis in osteosarcoma |
| url | https://doi.org/10.1038/s41598-024-51732-1 |
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