Heme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade Gliomas

Background: Gliomas are the most common tumors in human brains with unpleasing outcomes. Heme oxygenase-1 (HMOX1, HO-1) was a potential target for human cancers. However, their relationship remains incompletely discussed.Methods: We employed a total of 952 lower grade glioma (LGG) patients from TCGA...

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Autores principales:	Wenrui Ye, Zhixiong Liu, Fangkun Liu, Cong Luo
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	glioma heme oxygenase-1 prognosis risk signature single-cell sequencing Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d006b344c3cc44b28a4bf1c673588235
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spelling	oai:doaj.org-article:d006b344c3cc44b28a4bf1c6735882352021-11-09T13:00:51ZHeme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade Gliomas2296-634X10.3389/fcell.2021.760800https://doaj.org/article/d006b344c3cc44b28a4bf1c6735882352021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.760800/fullhttps://doaj.org/toc/2296-634XBackground: Gliomas are the most common tumors in human brains with unpleasing outcomes. Heme oxygenase-1 (HMOX1, HO-1) was a potential target for human cancers. However, their relationship remains incompletely discussed.Methods: We employed a total of 952 lower grade glioma (LGG) patients from TCGA and CGGA databases, and 29 samples in our hospital for subsequent analyses. Expression, mutational, survival, and immune profiles of HMOX1 were comprehensively evaluated. We constructed a risk signature using the LASSO Cox regression model, and further generated a nomogram model to predict survival of LGG patients. Single-cell transcriptomic sequencing data were also employed to investigated the role of HMOX1 in cancer cells.Results: We found that HMOX1 was overexpressed and was related to poorer survival in gliomas. HMOX1-related genes (HRGs) were involved in immune-related pathways. Patients in the high-risk group exhibited significantly poorer overall survival. The risk score was positively correlated with the abundance of resting memory CD4+ T cells, M1, M2 macrophages, and activated dendritic cells. Additionally, immunotherapy showed potent efficacy in low-risk group. And patients with lower HMOX1 expression were predicted to have better response to immunotherapies, suggesting that immunotherapies combined with HMOX1 inhibition may execute good responses. Moreover, significant correlations were found between HMOX1 expression and single-cell functional states including angiogenesis, hypoxia, and metastasis. Finally, we constructed a nomogram which could predict 1-, 3-, and 5-year survival in LGG patients.Conclusion:HMOX1 is involved in immune infiltration and predicts poor survival in patients with lower grade glioma. Importantly, HMOX1 were related to oncological functional states including angiogenesis, hypoxia, and metastasis. A nomogram integrated with the risk signature was obtained to robustly predict glioma patient outcomes, with the potential to guide clinical decision-making.Wenrui YeZhixiong LiuZhixiong LiuFangkun LiuCong LuoFrontiers Media S.A.articlegliomaheme oxygenase-1prognosisrisk signaturesingle-cell sequencingBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioma heme oxygenase-1 prognosis risk signature single-cell sequencing Biology (General) QH301-705.5
spellingShingle	glioma heme oxygenase-1 prognosis risk signature single-cell sequencing Biology (General) QH301-705.5 Wenrui Ye Zhixiong Liu Zhixiong Liu Fangkun Liu Cong Luo Heme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade Gliomas
description	Background: Gliomas are the most common tumors in human brains with unpleasing outcomes. Heme oxygenase-1 (HMOX1, HO-1) was a potential target for human cancers. However, their relationship remains incompletely discussed.Methods: We employed a total of 952 lower grade glioma (LGG) patients from TCGA and CGGA databases, and 29 samples in our hospital for subsequent analyses. Expression, mutational, survival, and immune profiles of HMOX1 were comprehensively evaluated. We constructed a risk signature using the LASSO Cox regression model, and further generated a nomogram model to predict survival of LGG patients. Single-cell transcriptomic sequencing data were also employed to investigated the role of HMOX1 in cancer cells.Results: We found that HMOX1 was overexpressed and was related to poorer survival in gliomas. HMOX1-related genes (HRGs) were involved in immune-related pathways. Patients in the high-risk group exhibited significantly poorer overall survival. The risk score was positively correlated with the abundance of resting memory CD4+ T cells, M1, M2 macrophages, and activated dendritic cells. Additionally, immunotherapy showed potent efficacy in low-risk group. And patients with lower HMOX1 expression were predicted to have better response to immunotherapies, suggesting that immunotherapies combined with HMOX1 inhibition may execute good responses. Moreover, significant correlations were found between HMOX1 expression and single-cell functional states including angiogenesis, hypoxia, and metastasis. Finally, we constructed a nomogram which could predict 1-, 3-, and 5-year survival in LGG patients.Conclusion:HMOX1 is involved in immune infiltration and predicts poor survival in patients with lower grade glioma. Importantly, HMOX1 were related to oncological functional states including angiogenesis, hypoxia, and metastasis. A nomogram integrated with the risk signature was obtained to robustly predict glioma patient outcomes, with the potential to guide clinical decision-making.
format	article
author	Wenrui Ye Zhixiong Liu Zhixiong Liu Fangkun Liu Cong Luo
author_facet	Wenrui Ye Zhixiong Liu Zhixiong Liu Fangkun Liu Cong Luo
author_sort	Wenrui Ye
title	Heme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade Gliomas
title_short	Heme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade Gliomas
title_full	Heme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade Gliomas
title_fullStr	Heme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade Gliomas
title_full_unstemmed	Heme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade Gliomas
title_sort	heme oxygenase-1 predicts risk stratification and immunotherapy efficacy in lower grade gliomas
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d006b344c3cc44b28a4bf1c673588235
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Heme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade Gliomas

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