Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms
Abstract Osteosarcoma (OS) is the most common primary malignant bone tumor with high metastatic potential and relapse risk. To study the regulatory mechanism of the OS microenvironment, a complex regulatory network involving the ferroptosis- and immune response-related genes remains to be establishe...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33009-1 |
| _version_ | 1827970523577974784 |
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| author | Guibin Li Jie Lei Dexin Xu Wenchang Yu Jinping Bai Ge Wu |
| author_facet | Guibin Li Jie Lei Dexin Xu Wenchang Yu Jinping Bai Ge Wu |
| author_sort | Guibin Li |
| collection | DOAJ |
| description | Abstract Osteosarcoma (OS) is the most common primary malignant bone tumor with high metastatic potential and relapse risk. To study the regulatory mechanism of the OS microenvironment, a complex regulatory network involving the ferroptosis- and immune response-related genes remains to be established. In the present study, we determined the effect of a comprehensive evaluation system established on the basis of ferroptosis- and immune-related genes on the immune status, related biomarkers, prognosis, and the potential regulatory networks underlying OS based on the TARGET and Gene Expression Omnibus databases that contain information on OS patients by bioinformatics analyses. We first characterized individual ferroptosis scores and immune scores through gene set variation analysis (GSVA) against TARGET-OS datasets. We then identified differentially expressed genes by score groups. Weighted gene co-expression network analysis was performed to identify the most relevant ferroptosis-related and immune-related gene modules, which facilitated the identification of 327 ferroptosis gene and 306 immune gene candidates. A 4-gene (WAS, CORT, WNT16, and GLB1L2) signature was constructed and valuation using the least absolute shrinkage and selection operator-Cox regression models to effectively predict OS prognosis. The prediction efficiency was further validated by GSE39055. We stratified patients based on the prognostic scoring systems. Eight hub genes (namely CD3D, CD8A, CD3E, IL2, CD2, MYH6, MYH7, and MYL2) were identified, and TF–miRNA target regulatory networks were constructed. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and GSVA were used to determine the signature’s potential pathways and biological functions, which showed that the hub genes were enriched in ferroptosis-associated biological functions and immune-associated molecular mechanisms. Thereafter, we investigated the proportion and infiltration extent of 22 infiltrating immune cells by using CIBERSORT, which revealed significant subgroup differences in CD8 + T cells, M0 macrophages, and M2 macrophages. In conclusion, we determined a new ferroptosis-related and immune-related gene signature for predicting OS patients’ prognosis and further explored the ferroptosis and immunity interactions during OS development, which provides insights into the exploration of molecular mechanisms and targeted therapies in patients with OS. |
| first_indexed | 2024-04-09T18:55:10Z |
| format | Article |
| id | doaj.art-ac7a055ae3a04e67b62200f4381aa65d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T18:55:10Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ac7a055ae3a04e67b62200f4381aa65d2023-04-09T11:13:28ZengNature PortfolioScientific Reports2045-23222023-04-0113111610.1038/s41598-023-33009-1Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanismsGuibin Li0Jie Lei1Dexin Xu2Wenchang Yu3Jinping Bai4Ge Wu5Department of Orthopaedics, Jilin Province FAW General HospitalDepartment of Hospital affairs, Jilin Province FAW General HospitalDepartment of Orthopaedics, Jilin Province FAW General HospitalDepartment of Drug management, Jilin Province FAW General HospitalChronic disease outpatient service, Jilin Province FAW General HospitalDepartment of Clinical Pharmacy, Jilin Province FAW General HospitalAbstract Osteosarcoma (OS) is the most common primary malignant bone tumor with high metastatic potential and relapse risk. To study the regulatory mechanism of the OS microenvironment, a complex regulatory network involving the ferroptosis- and immune response-related genes remains to be established. In the present study, we determined the effect of a comprehensive evaluation system established on the basis of ferroptosis- and immune-related genes on the immune status, related biomarkers, prognosis, and the potential regulatory networks underlying OS based on the TARGET and Gene Expression Omnibus databases that contain information on OS patients by bioinformatics analyses. We first characterized individual ferroptosis scores and immune scores through gene set variation analysis (GSVA) against TARGET-OS datasets. We then identified differentially expressed genes by score groups. Weighted gene co-expression network analysis was performed to identify the most relevant ferroptosis-related and immune-related gene modules, which facilitated the identification of 327 ferroptosis gene and 306 immune gene candidates. A 4-gene (WAS, CORT, WNT16, and GLB1L2) signature was constructed and valuation using the least absolute shrinkage and selection operator-Cox regression models to effectively predict OS prognosis. The prediction efficiency was further validated by GSE39055. We stratified patients based on the prognostic scoring systems. Eight hub genes (namely CD3D, CD8A, CD3E, IL2, CD2, MYH6, MYH7, and MYL2) were identified, and TF–miRNA target regulatory networks were constructed. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and GSVA were used to determine the signature’s potential pathways and biological functions, which showed that the hub genes were enriched in ferroptosis-associated biological functions and immune-associated molecular mechanisms. Thereafter, we investigated the proportion and infiltration extent of 22 infiltrating immune cells by using CIBERSORT, which revealed significant subgroup differences in CD8 + T cells, M0 macrophages, and M2 macrophages. In conclusion, we determined a new ferroptosis-related and immune-related gene signature for predicting OS patients’ prognosis and further explored the ferroptosis and immunity interactions during OS development, which provides insights into the exploration of molecular mechanisms and targeted therapies in patients with OS.https://doi.org/10.1038/s41598-023-33009-1 |
| spellingShingle | Guibin Li Jie Lei Dexin Xu Wenchang Yu Jinping Bai Ge Wu Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms Scientific Reports |
| title | Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms |
| title_full | Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms |
| title_fullStr | Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms |
| title_full_unstemmed | Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms |
| title_short | Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms |
| title_sort | integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms |
| url | https://doi.org/10.1038/s41598-023-33009-1 |
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