Abnormal signal pathways and tumor heterogeneity in osteosarcoma
Abstract Background Osteosarcoma (OS) is the most frequent and aggressive primary malignant sarcoma among adolescents and chemotherapy has not substantially progressed for decades. New insights into OS development and therapeutic strategies are urgently needed. Methods We analyzed integrated single-...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-03961-7 |
| _version_ | 1811165746041978880 |
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| author | Yifeng Sun Chunming Zhang Qiongxuan Fang Wenqiang Zhang Wei Liu |
| author_facet | Yifeng Sun Chunming Zhang Qiongxuan Fang Wenqiang Zhang Wei Liu |
| author_sort | Yifeng Sun |
| collection | DOAJ |
| description | Abstract Background Osteosarcoma (OS) is the most frequent and aggressive primary malignant sarcoma among adolescents and chemotherapy has not substantially progressed for decades. New insights into OS development and therapeutic strategies are urgently needed. Methods We analyzed integrated single-cell transcriptomes, bulk RNA-seq, and microarray data from Gene Expression Omnibus (GEO) datasets. We also used Weighted Gene Co-expression Network Analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), along with Simple ClinVar and Enrichr web servers. Results The findings of integrated single-cell analysis showed that OS arises from imperfect osteogenesis during development. Novel abnormalities comprised deficient TGFβ and P53 signal pathways, and cell cycle pathway activation, and a potentially new driver mutation in the interferon induced transmembrane protein 5 (IFITM5) that might function as a pathogenic factor in OS. Osteosarcoma is characterized by oncocyte heterogeneity, especially in immunogenic and adipocyte-like subtypes that respectively promote and hamper OS treatment. Etoposide is a promising chemotherapeutic that provides palliation by affecting the subtype of OS and correcting the abnormal pathways. Conclusion Various abnormal signal pathways play indispensable roles in OS development. We explored the heterogeneity and underlying mechanisms of OS and generated findings that will assist with OS assessment and selecting optimal therapies. |
| first_indexed | 2024-04-10T15:41:38Z |
| format | Article |
| id | doaj.art-0625ae2336bd4925987f227c99a82daf |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-10T15:41:38Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-0625ae2336bd4925987f227c99a82daf2023-02-12T12:20:53ZengBMCJournal of Translational Medicine1479-58762023-02-0121111410.1186/s12967-023-03961-7Abnormal signal pathways and tumor heterogeneity in osteosarcomaYifeng Sun0Chunming Zhang1Qiongxuan Fang2Wenqiang Zhang3Wei Liu4Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational MedicineDepartment of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational MedicineMOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking UniversityDepartment of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational MedicineDepartment of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational MedicineAbstract Background Osteosarcoma (OS) is the most frequent and aggressive primary malignant sarcoma among adolescents and chemotherapy has not substantially progressed for decades. New insights into OS development and therapeutic strategies are urgently needed. Methods We analyzed integrated single-cell transcriptomes, bulk RNA-seq, and microarray data from Gene Expression Omnibus (GEO) datasets. We also used Weighted Gene Co-expression Network Analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), along with Simple ClinVar and Enrichr web servers. Results The findings of integrated single-cell analysis showed that OS arises from imperfect osteogenesis during development. Novel abnormalities comprised deficient TGFβ and P53 signal pathways, and cell cycle pathway activation, and a potentially new driver mutation in the interferon induced transmembrane protein 5 (IFITM5) that might function as a pathogenic factor in OS. Osteosarcoma is characterized by oncocyte heterogeneity, especially in immunogenic and adipocyte-like subtypes that respectively promote and hamper OS treatment. Etoposide is a promising chemotherapeutic that provides palliation by affecting the subtype of OS and correcting the abnormal pathways. Conclusion Various abnormal signal pathways play indispensable roles in OS development. We explored the heterogeneity and underlying mechanisms of OS and generated findings that will assist with OS assessment and selecting optimal therapies.https://doi.org/10.1186/s12967-023-03961-7OsteosarcomaAbnormal signal pathwayChemotherapyOncocyte heterogeneity |
| spellingShingle | Yifeng Sun Chunming Zhang Qiongxuan Fang Wenqiang Zhang Wei Liu Abnormal signal pathways and tumor heterogeneity in osteosarcoma Journal of Translational Medicine Osteosarcoma Abnormal signal pathway Chemotherapy Oncocyte heterogeneity |
| title | Abnormal signal pathways and tumor heterogeneity in osteosarcoma |
| title_full | Abnormal signal pathways and tumor heterogeneity in osteosarcoma |
| title_fullStr | Abnormal signal pathways and tumor heterogeneity in osteosarcoma |
| title_full_unstemmed | Abnormal signal pathways and tumor heterogeneity in osteosarcoma |
| title_short | Abnormal signal pathways and tumor heterogeneity in osteosarcoma |
| title_sort | abnormal signal pathways and tumor heterogeneity in osteosarcoma |
| topic | Osteosarcoma Abnormal signal pathway Chemotherapy Oncocyte heterogeneity |
| url | https://doi.org/10.1186/s12967-023-03961-7 |
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