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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.

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