Clinical characterization, genetic profile, and epigenetic regulation of TOX in diffuse gliomas

Abstract

Background Multiple studies focusing on immune therapy towards glioblastoma (GBM) have attained great successes. TOX has been found to be closely related to immune environment surrounding tumors, while the expression of TOX has not been fully understood in gliomas. Methods Mining data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed 1691 WHO grade I-IV human glioma samples with transcriptome data. R language was used for most statistical analysis. Somatic mutations and somatic copy number variation (CNV) were analyzed using GISTIC 2.0.Results TOX was down-regulated in malignant gliomas, especially in the proneural and isocitrate dehydrogenase (IDH) mutant subtypes of GBM. TOX low tumours are related to loss of PTEN and amplification of EGFR, while TOX high tumours harbor mutations in IDH1 (91%). TOX was highly expressed in cellular tumour, leading edge regions. TOX was enriched in multiple immune related processes including lymphocytes migration in GBM in gene ontology and pathway analysis. Finally, TOX had negative association with the infiltration of several immune cell types in tumour microenvironment in cell lineage analysis. Conclusion TOX has the potential to be a new target for immune-therapy or a prognostic marker for GBM.