RT Journal Article SR Electronic T1 Omics-based integrated analysis identified ATRX as a biomarker associated with glioma diagnosis and prognosis JF Cancer Biology and Medicine JO Cancer Biol Med FD China Anti-Cancer Association SP 784 OP 796 DO 10.20892/j.issn.2095-3941.2019.0143 VO 16 IS 4 A1 Yingbin Xie A1 Yanli Tan A1 Chao Yang A1 Xuehao Zhang A1 Can Xu A1 Xiaoxia Qiao A1 Jianglong Xu A1 Shaohui Tian A1 Chuan Fang A1 Chunsheng Kang YR 2019 UL http://www.cancerbiomed.org/content/16/4/784.abstract AB Objective ATRX is a multifunctional protein that is tightly regulated by and implicated in transcriptional regulation and chromatin remodeling. Numerous studies have shown that genetic alterations in ATRX play a significant role in gliomas. This study aims to further determine the relationship between ATRX and glioma prognosis and identify possible mechanisms for exploring the biological significance of ATRX using large data sets.Methods We used The Cancer Genome Atlas (TCGA) database and 130 immunohistochemical results to confirm the difference in ATRX mutations in high- and low-grade gliomas. An online analysis of the TCGA glioma datasets using the cBioPortal platform was performed to study the relationship between ATRX mutations and IDH1, TP53, CDKN2A and CDKN2B mutations in the corresponding TCGA glioma dataset. In combination with clinical pathology data, the biological significance of the relationships were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and annotations of all adjacent genes in the network were performedin the Database for Annotation, Visualization and Integrated Discovery (DAVID) and R language. A protein-protein interaction (PPI) network was constructed, and the interactions of all adjacent nodes were analyzed by the String database and using Cytoscape software.Results In the selected TCGA glioma datasets, a total of 2,228 patients were queried, 21% of whom had ATRX alterations, which co-occurred frequently with TP53 and IDH1 mutations. ATRX alterations are associated with multiple critical molecular events, which results in a significantly improved overall survival (OS) rate. In low-grade gliomas, ATRX mutations are significantly associated with multiple important molecular events, such as ZNF274 and FDXR at mRNA and protein levels. A functional cluster analysis revealed that these genes played a role in chromatin binding and P53, and a link was observed between ATRX and IDH1 and TP53 in the interaction network. ATRX and TP53 are important nodes in the network and have potential links with the blood oxygen imbalance.Conclusions ATRX mutations have clinical implications for the molecular diagnosis of gliomas and can provide diagnostic and prognostic information for gliomas. ATRX is expected to serve as a new therapeutic target.