Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for Osteosarcoma
Objective: Hypoxic tumors contribute to local failure and distant metastases. Nevertheless, the molecular hallmarks of hypoxia remain ill-defined in osteosarcoma. Here, we developed a hypoxic gene signature in osteosarcoma prognoses.Methods: With the random survival forest algorithm, a prognostic hy...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.705148/full |
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| author | Fengfeng Wu Juntao Xu Mingchao Jin Xuesheng Jiang Jianyou Li Xiongfeng Li Zhuo Chen Jiangbo Nie Zhipeng Meng Guorong Wang |
| author_facet | Fengfeng Wu Juntao Xu Mingchao Jin Xuesheng Jiang Jianyou Li Xiongfeng Li Zhuo Chen Jiangbo Nie Zhipeng Meng Guorong Wang |
| author_sort | Fengfeng Wu |
| collection | DOAJ |
| description | Objective: Hypoxic tumors contribute to local failure and distant metastases. Nevertheless, the molecular hallmarks of hypoxia remain ill-defined in osteosarcoma. Here, we developed a hypoxic gene signature in osteosarcoma prognoses.Methods: With the random survival forest algorithm, a prognostic hypoxia-related gene signature was constructed for osteosarcoma in the TARGET cohort. Overall survival (OS) analysis, receiver operating characteristic (ROC) curve, multivariate cox regression analysis, and subgroup analysis were utilized for assessing the predictive efficacy of this signature. Also, external validation was presented in the GSE21257 cohort. GSEA was applied for signaling pathways involved in the high- and low-risk samples. Correlation analyses between risk score and immune cells, stromal/immune score, immune checkpoints, and sensitivity of chemotherapy drugs were performed in osteosarcoma. Then, a nomogram was built by integrating risk score, age, and gender.Results: A five-hypoxic gene signature was developed for predicting survival outcomes of osteosarcoma patients. ROC curves confirmed that this signature possessed the well predictive performance on osteosarcoma prognosis. Furthermore, it could be independently predictive of prognosis. Metabolism of xenobiotics by cytochrome P450 and nitrogen metabolism were activated in the high-risk samples while cell adhesion molecules cams and intestinal immune network for IgA production were enriched in the low-risk samples. The low-risk samples were characterized by elevated immune cell infiltrations, stromal/immune scores, TNFRSF4 expression, and sensitivity to cisplatin. The nomogram accurately predicted 1-, 3-, and 5-years survival duration.Conclusion: These findings might offer an insight into the optimization of prognosis risk stratification and individualized therapy for osteosarcoma patients. |
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| language | English |
| last_indexed | 2024-12-20T15:41:02Z |
| publishDate | 2022-01-01 |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-9ee050af0e724d3ca1c65943d20edaea2022-12-21T19:35:11ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-01-01810.3389/fmolb.2021.705148705148Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for OsteosarcomaFengfeng Wu0Juntao Xu1Mingchao Jin2Xuesheng Jiang3Jianyou Li4Xiongfeng Li5Zhuo Chen6Jiangbo Nie7Zhipeng Meng8Guorong Wang9Department of Orthopedics and Rehabilitation, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, ChinaDepartment of Orthopedics, Huzhou Traditional Chinese Medicine Hospital, Affiliated to Zhejiang Chinese Medical University, Huzhou, ChinaDepartment of Orthopedics, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, ChinaDepartment of Orthopedics, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, ChinaDepartment of Orthopedics, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, ChinaDepartment of Orthopedics, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, ChinaDepartment of Orthopedics, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, ChinaDepartment of Orthopedics, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, ChinaDepartment of Anesthesiology, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, ChinaDepartment of Orthopedics, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang University Huzhou Hospital, Huzhou, ChinaObjective: Hypoxic tumors contribute to local failure and distant metastases. Nevertheless, the molecular hallmarks of hypoxia remain ill-defined in osteosarcoma. Here, we developed a hypoxic gene signature in osteosarcoma prognoses.Methods: With the random survival forest algorithm, a prognostic hypoxia-related gene signature was constructed for osteosarcoma in the TARGET cohort. Overall survival (OS) analysis, receiver operating characteristic (ROC) curve, multivariate cox regression analysis, and subgroup analysis were utilized for assessing the predictive efficacy of this signature. Also, external validation was presented in the GSE21257 cohort. GSEA was applied for signaling pathways involved in the high- and low-risk samples. Correlation analyses between risk score and immune cells, stromal/immune score, immune checkpoints, and sensitivity of chemotherapy drugs were performed in osteosarcoma. Then, a nomogram was built by integrating risk score, age, and gender.Results: A five-hypoxic gene signature was developed for predicting survival outcomes of osteosarcoma patients. ROC curves confirmed that this signature possessed the well predictive performance on osteosarcoma prognosis. Furthermore, it could be independently predictive of prognosis. Metabolism of xenobiotics by cytochrome P450 and nitrogen metabolism were activated in the high-risk samples while cell adhesion molecules cams and intestinal immune network for IgA production were enriched in the low-risk samples. The low-risk samples were characterized by elevated immune cell infiltrations, stromal/immune scores, TNFRSF4 expression, and sensitivity to cisplatin. The nomogram accurately predicted 1-, 3-, and 5-years survival duration.Conclusion: These findings might offer an insight into the optimization of prognosis risk stratification and individualized therapy for osteosarcoma patients.https://www.frontiersin.org/articles/10.3389/fmolb.2021.705148/fullosteosarcomaprognosishypoxiagene signatureimmune microenvironmentnomogram |
| spellingShingle | Fengfeng Wu Juntao Xu Mingchao Jin Xuesheng Jiang Jianyou Li Xiongfeng Li Zhuo Chen Jiangbo Nie Zhipeng Meng Guorong Wang Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for Osteosarcoma Frontiers in Molecular Biosciences osteosarcoma prognosis hypoxia gene signature immune microenvironment nomogram |
| title | Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for Osteosarcoma |
| title_full | Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for Osteosarcoma |
| title_fullStr | Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for Osteosarcoma |
| title_full_unstemmed | Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for Osteosarcoma |
| title_short | Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for Osteosarcoma |
| title_sort | development and verification of a hypoxic gene signature for predicting prognosis immune microenvironment and chemosensitivity for osteosarcoma |
| topic | osteosarcoma prognosis hypoxia gene signature immune microenvironment nomogram |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.705148/full |
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