Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas

Abstract Background Immunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood. Methods Using data from The Cancer Genome Atlas (TCGA)...

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Main Authors: Hao Zhang, Fan Fan, Yuanqiang Yu, Zeyu Wang, Fangkun Liu, Ziyu Dai, Liyang Zhang, Zhixiong Liu, Quan Cheng
Format: Article
Language:English
Published: BMC 2020-08-01
Series:Journal of Translational Medicine
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12967-020-02460-3
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author Hao Zhang
Fan Fan
Yuanqiang Yu
Zeyu Wang
Fangkun Liu
Ziyu Dai
Liyang Zhang
Zhixiong Liu
Quan Cheng
author_facet Hao Zhang
Fan Fan
Yuanqiang Yu
Zeyu Wang
Fangkun Liu
Ziyu Dai
Liyang Zhang
Zhixiong Liu
Quan Cheng
author_sort Hao Zhang
collection DOAJ
description Abstract Background Immunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood. Methods Using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed the transcriptomes of 1691 WHO grade I-IV human glioma samples. The R language was used to perform most of the statistical analyses. Somatic mutations and somatic copy number variation (CNV) were analyzed using GISTIC 2.0. Results TOX was down-regulated in malignant gliomas compared to low grade gliomas, and upregulated in the proneural and IDH mutant subtypes of GBM. TOXlow tumours are associated with the loss of PTEN and amplification of EGFR, while TOXhigh tumours harbor frequent mutations in IDH1 (91%). TOX was highly expressed in leading edge regions of tumours. Gene ontology and pathway analyses demonstrated that TOX was enriched in multiple immune related processes including lymphocyte migration in GBM. Finally, TOX had a negative association with the infiltration of several immune cell types in the tumour microenvironment. Conclusion TOX has the potential to be a new prognostic marker for GBM.
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spelling doaj.art-8a3f4bd9861140bcb41d8ed27d377c2f2022-12-22T00:58:16ZengBMCJournal of Translational Medicine1479-58762020-08-0118111610.1186/s12967-020-02460-3Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomasHao Zhang0Fan Fan1Yuanqiang Yu2Zeyu Wang3Fangkun Liu4Ziyu Dai5Liyang Zhang6Zhixiong Liu7Quan Cheng8Department of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityAbstract Background Immunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood. Methods Using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed the transcriptomes of 1691 WHO grade I-IV human glioma samples. The R language was used to perform most of the statistical analyses. Somatic mutations and somatic copy number variation (CNV) were analyzed using GISTIC 2.0. Results TOX was down-regulated in malignant gliomas compared to low grade gliomas, and upregulated in the proneural and IDH mutant subtypes of GBM. TOXlow tumours are associated with the loss of PTEN and amplification of EGFR, while TOXhigh tumours harbor frequent mutations in IDH1 (91%). TOX was highly expressed in leading edge regions of tumours. Gene ontology and pathway analyses demonstrated that TOX was enriched in multiple immune related processes including lymphocyte migration in GBM. Finally, TOX had a negative association with the infiltration of several immune cell types in the tumour microenvironment. Conclusion TOX has the potential to be a new prognostic marker for GBM.http://link.springer.com/article/10.1186/s12967-020-02460-3GliomaTOXInflammatory activityImmune responsePrognosis
spellingShingle Hao Zhang
Fan Fan
Yuanqiang Yu
Zeyu Wang
Fangkun Liu
Ziyu Dai
Liyang Zhang
Zhixiong Liu
Quan Cheng
Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas
Journal of Translational Medicine
Glioma
TOX
Inflammatory activity
Immune response
Prognosis
title Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas
title_full Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas
title_fullStr Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas
title_full_unstemmed Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas
title_short Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas
title_sort clinical characterization genetic profiling and immune infiltration of tox in diffuse gliomas
topic Glioma
TOX
Inflammatory activity
Immune response
Prognosis
url http://link.springer.com/article/10.1186/s12967-020-02460-3
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