A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas

Most solid tumours are hypoxic. Tumour cell proliferation and metabolism accelerate oxygen consumption. The low oxygen supply due to vascular abnormalisation and the high oxygen demand of tumour cells give rise to an imbalance, resulting in tumour hypoxia. Hypoxia alters cellular behaviour and is as...

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Autores principales:	Feng Gao, Zhengzheng Wang, Jiajie Gu, Xiaojia Zhang, Huixiao Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	hypoxia glioma risk prediction model Cox regression ubiquitin–proteasome system Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/38e886e1287b496f80fe6d67e246183f
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spelling	oai:doaj.org-article:38e886e1287b496f80fe6d67e246183f2021-11-12T05:23:38ZA Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas2234-943X10.3389/fonc.2021.726794https://doaj.org/article/38e886e1287b496f80fe6d67e246183f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.726794/fullhttps://doaj.org/toc/2234-943XMost solid tumours are hypoxic. Tumour cell proliferation and metabolism accelerate oxygen consumption. The low oxygen supply due to vascular abnormalisation and the high oxygen demand of tumour cells give rise to an imbalance, resulting in tumour hypoxia. Hypoxia alters cellular behaviour and is associated with extracellular matrix remodelling, enhanced tumour migration, and metastatic behaviour. In light of the foregoing, more research on the progressive and prognostic impacts of hypoxia on gliomas are crucial. In this study, we analysed the expression levels of 75 hypoxia-related genes in gliomas and found that a total of 26 genes were differentially expressed in The Cancer Genome Atlas (TCGA) database samples. We also constructed protein–protein interaction networks using the STRING database and Cytoscape. We obtained a total of 10 Hub genes using the MCC algorithm screening in the cytoHubba plugin. A prognostic risk model with seven gene signatures (PSMB6, PSMD9, UBB, PSMD12, PSMB10, PSMA5, and PSMD14) was constructed based on the 10 Hub genes using LASSO–Cox regression analysis. The model was verified to be highly accurate using subject work characteristic curves. The seven-gene signatures were then analysed by univariate and multivariate Cox. Notably, PSMB10, PSMD12, UBB, PSMA5, and PSMB6 were found to be independent prognostic predictive markers for glioma. In addition, PSMB6, PSMA5, UBB, and PSMD12 were lowly expressed, while PSMB10 was highly expressed, in the TCGA and GTEx integrated glioma samples and normal samples, which were verified through protein expression levels in the Human Protein Atlas database. This study found the prognostic predictive values of the hypoxia-related genes PSMB10, PSMD12, UBB, PSMA5, and PSMB6 for glioma and provided ideas and entry points for the progress of hypoxia-related glioma.Feng GaoZhengzheng WangJiajie GuXiaojia ZhangHuixiao WangFrontiers Media S.A.articlehypoxiagliomarisk prediction modelCox regressionubiquitin–proteasome systemNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypoxia glioma risk prediction model Cox regression ubiquitin–proteasome system Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hypoxia glioma risk prediction model Cox regression ubiquitin–proteasome system Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Feng Gao Zhengzheng Wang Jiajie Gu Xiaojia Zhang Huixiao Wang A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas
description	Most solid tumours are hypoxic. Tumour cell proliferation and metabolism accelerate oxygen consumption. The low oxygen supply due to vascular abnormalisation and the high oxygen demand of tumour cells give rise to an imbalance, resulting in tumour hypoxia. Hypoxia alters cellular behaviour and is associated with extracellular matrix remodelling, enhanced tumour migration, and metastatic behaviour. In light of the foregoing, more research on the progressive and prognostic impacts of hypoxia on gliomas are crucial. In this study, we analysed the expression levels of 75 hypoxia-related genes in gliomas and found that a total of 26 genes were differentially expressed in The Cancer Genome Atlas (TCGA) database samples. We also constructed protein–protein interaction networks using the STRING database and Cytoscape. We obtained a total of 10 Hub genes using the MCC algorithm screening in the cytoHubba plugin. A prognostic risk model with seven gene signatures (PSMB6, PSMD9, UBB, PSMD12, PSMB10, PSMA5, and PSMD14) was constructed based on the 10 Hub genes using LASSO–Cox regression analysis. The model was verified to be highly accurate using subject work characteristic curves. The seven-gene signatures were then analysed by univariate and multivariate Cox. Notably, PSMB10, PSMD12, UBB, PSMA5, and PSMB6 were found to be independent prognostic predictive markers for glioma. In addition, PSMB6, PSMA5, UBB, and PSMD12 were lowly expressed, while PSMB10 was highly expressed, in the TCGA and GTEx integrated glioma samples and normal samples, which were verified through protein expression levels in the Human Protein Atlas database. This study found the prognostic predictive values of the hypoxia-related genes PSMB10, PSMD12, UBB, PSMA5, and PSMB6 for glioma and provided ideas and entry points for the progress of hypoxia-related glioma.
format	article
author	Feng Gao Zhengzheng Wang Jiajie Gu Xiaojia Zhang Huixiao Wang
author_facet	Feng Gao Zhengzheng Wang Jiajie Gu Xiaojia Zhang Huixiao Wang
author_sort	Feng Gao
title	A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas
title_short	A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas
title_full	A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas
title_fullStr	A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas
title_full_unstemmed	A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas
title_sort	hypoxia-associated prognostic gene signature risk model and prognosis predictors in gliomas
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/38e886e1287b496f80fe6d67e246183f
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A Hypoxia-Associated Prognostic Gene Signature Risk Model and Prognosis Predictors in Gliomas

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