Omics-based integrated analysis identified ATRX as a biomarker associated with glioma diagnosis and prognosis

Yingbin Xie, Yanli Tan, Chao Yang, et al.

Abstract


Objective: ATRX is a multifunctional protein that is tightly regulated by and implicated in transcriptional regulation andchromatin remodeling. Numerous studies have shown that genetic alterations in ATRX play a significant role in gliomas. Thisstudy aims to further determine the relationship between ATRX and glioma prognosis and identify possible mechanisms forexploring 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 differencein ATRX mutations in high- and low-grade gliomas. An online analysis of the TCGA glioma datasets using the cBioPortal platformwas performed to study the relationship between ATRX mutations and IDH1, TP53, CDKN2A and CDKN2B mutations in thecorresponding TCGA glioma dataset. In combination with clinical pathology data, the biological significance of the relationshipswere analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and annotationsof all adjacent genes in the network were performed 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 nodeswere 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, whichco-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 significantlyassociated with multiple important molecular events, such as ZNF274 and FDXR at mRNA and protein levels. A functional clusteranalysis revealed that these genes played a role in chromatin binding and P53, and a link was observed between ATRX and IDH1and TP53 in the interaction network. ATRX and TP53 are important nodes in the network and have potential links with the bloodoxygen imbalance.

Conclusions: ATRX mutations have clinical implications for the molecular diagnosis of gliomas and can provide diagnostic andprognostic information for gliomas. ATRX is expected to serve as a new therapeutic target.

Cite this article as: Xie Y, Tan Y, Yang C, Zhang X, Xu C, Qiao X, et al.Omics-based integrated analysis identified ATRX as a biomarker associatedwith glioma diagnosis and prognosis. Cancer Biol Med. 2019; 16: 784-96. doi:10.20892/j.issn.2095-3941.2019.0143


Keywords


ATRX; mutation; copy number variation; glioma; biomarkers

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