Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas
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Journal of Translational Medicine Open Access
RESEARCH
Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas Hao Zhang1,4†, Fan Fan1,3,4†, Yuanqiang Yu1,4, Zeyu Wang1,4, Fangkun Liu1,4, Ziyu Dai1,4, Liyang Zhang1,4,5,6*, Zhixiong Liu1,4* and Quan Cheng1,2,4*
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. Keywords: Glioma, TOX, Inflammatory activity, Immune response, Prognosis Background Gliomas continue to be the most common and devastating primary brain tumor. Despite multiple conventional therapies, including radiotherapy with adjuvant temozolomide chemotherapy after resection [1, 2], patients with LGG (low grade glioma) have a median overall *Correspondence: [email protected]; [email protected]; [email protected] † Zhang Hao and Fan Fan contributed equally to this work 1 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of China 2 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of China Full list of author information is available at the end of the article
survival (OS) of 8–10 years, while patients with GBM (glioblastoma multi-form) have a dismal OS of less than 15 months [3, 4]. Therefore, new therapeutic approaches are desperately needed. Under normal physiological circumstances, immune checkpoints have proven to be responsible for the immune system self-tolerance [5, 6]. Recently, strategies eliciting immune responses against tumors have demonstrated breakthroughs in several cancer types [7–9]. One previous study demonstrated that tumor microenvironment, including infiltrating immune cells, play critical roles in supporting glioma progression [10]. Subsequent glioma immunotherapy research portends a p
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