Hypoxia-immune-related microenvironment prognostic signature for osteosarcoma

Introduction: Increasing evidences have shown that hypoxia and the immune microenvironment play vital roles in the development of osteosarcoma. However, reliable gene signatures based on the combination of hypoxia and the immune status for prognostic prediction of osteosarcoma have so far not been i...

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Main Authors: Wenshuo Zhang, Pang Lyu, Darja Andreev, Yewei Jia, Fulin Zhang, Aline Bozec
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.974851/full
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author Wenshuo Zhang
Pang Lyu
Darja Andreev
Yewei Jia
Fulin Zhang
Aline Bozec
author_facet Wenshuo Zhang
Pang Lyu
Darja Andreev
Yewei Jia
Fulin Zhang
Aline Bozec
author_sort Wenshuo Zhang
collection DOAJ
description Introduction: Increasing evidences have shown that hypoxia and the immune microenvironment play vital roles in the development of osteosarcoma. However, reliable gene signatures based on the combination of hypoxia and the immune status for prognostic prediction of osteosarcoma have so far not been identified.Methods: The individual hypoxia and immune status of osteosarcoma patients were identified with transcriptomic profiles of a training cohort from the TARGET database using ssGSEA and ESTIMATE algorithms, respectively. Lasso regression and stepwise Cox regression were performed to develop a hypoxia-immune-based gene signature. An independent cohort from the GEO database was used for external validation. Finally, a nomogram was constructed based on the gene signature and clinical features to improve the risk stratification and to quantify the risk assessment for individual patients.Results: Hypoxia and the immune status were significantly associated with the prognosis of osteosarcoma patients. Seven hypoxia- and immune-related genes (BNIP3, SLC38A5, SLC5A3, CKMT2, S100A3, CXCL11 and PGM1) were identified to be involved in our prognostic signature. In the training cohort, the prognostic signature discriminated high-risk patients with osteosarcoma. The hypoxia-immune-based gene signature proved to be a stable and predictive method as determined in different datasets and subgroups of patients. Furthermore, a nomogram based on the prognostic signature was generated to optimize the risk stratification and to quantify the risk assessment. Similar results were validated in an independent GEO cohort, confirming the stability and reliability of the prognostic signature.Conclusion: The hypoxia-immune-based prognostic signature might contribute to the optimization of risk stratification for survival and personalized management of osteosarcoma patients.
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spelling doaj.art-fbe90a244a8f4b7cb46536e21bc1bcc42022-12-22T04:19:30ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-12-011010.3389/fcell.2022.974851974851Hypoxia-immune-related microenvironment prognostic signature for osteosarcomaWenshuo ZhangPang LyuDarja AndreevYewei JiaFulin ZhangAline BozecIntroduction: Increasing evidences have shown that hypoxia and the immune microenvironment play vital roles in the development of osteosarcoma. However, reliable gene signatures based on the combination of hypoxia and the immune status for prognostic prediction of osteosarcoma have so far not been identified.Methods: The individual hypoxia and immune status of osteosarcoma patients were identified with transcriptomic profiles of a training cohort from the TARGET database using ssGSEA and ESTIMATE algorithms, respectively. Lasso regression and stepwise Cox regression were performed to develop a hypoxia-immune-based gene signature. An independent cohort from the GEO database was used for external validation. Finally, a nomogram was constructed based on the gene signature and clinical features to improve the risk stratification and to quantify the risk assessment for individual patients.Results: Hypoxia and the immune status were significantly associated with the prognosis of osteosarcoma patients. Seven hypoxia- and immune-related genes (BNIP3, SLC38A5, SLC5A3, CKMT2, S100A3, CXCL11 and PGM1) were identified to be involved in our prognostic signature. In the training cohort, the prognostic signature discriminated high-risk patients with osteosarcoma. The hypoxia-immune-based gene signature proved to be a stable and predictive method as determined in different datasets and subgroups of patients. Furthermore, a nomogram based on the prognostic signature was generated to optimize the risk stratification and to quantify the risk assessment. Similar results were validated in an independent GEO cohort, confirming the stability and reliability of the prognostic signature.Conclusion: The hypoxia-immune-based prognostic signature might contribute to the optimization of risk stratification for survival and personalized management of osteosarcoma patients.https://www.frontiersin.org/articles/10.3389/fcell.2022.974851/fullosteosarcomahypoxiaimmune statusprognosisbioinformatic analysis
spellingShingle Wenshuo Zhang
Pang Lyu
Darja Andreev
Yewei Jia
Fulin Zhang
Aline Bozec
Hypoxia-immune-related microenvironment prognostic signature for osteosarcoma
Frontiers in Cell and Developmental Biology
osteosarcoma
hypoxia
immune status
prognosis
bioinformatic analysis
title Hypoxia-immune-related microenvironment prognostic signature for osteosarcoma
title_full Hypoxia-immune-related microenvironment prognostic signature for osteosarcoma
title_fullStr Hypoxia-immune-related microenvironment prognostic signature for osteosarcoma
title_full_unstemmed Hypoxia-immune-related microenvironment prognostic signature for osteosarcoma
title_short Hypoxia-immune-related microenvironment prognostic signature for osteosarcoma
title_sort hypoxia immune related microenvironment prognostic signature for osteosarcoma
topic osteosarcoma
hypoxia
immune status
prognosis
bioinformatic analysis
url https://www.frontiersin.org/articles/10.3389/fcell.2022.974851/full
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AT panglyu hypoxiaimmunerelatedmicroenvironmentprognosticsignatureforosteosarcoma
AT darjaandreev hypoxiaimmunerelatedmicroenvironmentprognosticsignatureforosteosarcoma
AT yeweijia hypoxiaimmunerelatedmicroenvironmentprognosticsignatureforosteosarcoma
AT fulinzhang hypoxiaimmunerelatedmicroenvironmentprognosticsignatureforosteosarcoma
AT alinebozec hypoxiaimmunerelatedmicroenvironmentprognosticsignatureforosteosarcoma