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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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.760800/full |
| _version_ | 1818752314854342656 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T04:49:30Z |
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| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-18T04:49:30Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-d006b344c3cc44b28a4bf1c6735882352022-12-21T21:20:28ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-11-01910.3389/fcell.2021.760800760800Heme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade GliomasWenrui Ye0Zhixiong Liu1Zhixiong Liu2Fangkun Liu3Cong Luo4Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University (CSU), Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University (CSU), Changsha, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.760800/fullgliomaheme oxygenase-1prognosisrisk signaturesingle-cell sequencing |
| spellingShingle | Wenrui Ye Zhixiong Liu Zhixiong Liu Fangkun Liu Cong Luo Heme Oxygenase-1 Predicts Risk Stratification and Immunotherapy Efficacy in Lower Grade Gliomas Frontiers in Cell and Developmental Biology glioma heme oxygenase-1 prognosis risk signature single-cell sequencing |
| title | 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_short | 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 |
| topic | glioma heme oxygenase-1 prognosis risk signature single-cell sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.760800/full |
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