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

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,CDKN2 A and CDKN2 B 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.

The effect of umbrella-type branching on the blood circulation and tumor targeting of star-branched PLA-PMPC copolymer micelles

The effect of branching on the blood circulation and tumor targeting of polymer nanovehicles in vivo was investigated in this study. For the purpose, star-branched poly(lactic acid) and poly(2-methacryloyloxyethyl phosphorylcholine)(PLA-PMPC)copolymers with umbrella-type AB3,(AB3)_(2), and(AB3)_(3) architecture were synthesized by branching at the PLA core. Micelles self-assembled from these copolymers were used to evaluate the effect of core branching on blood circulation and tumor targeting. The results showed that branching changed the behavior of polymeric self-assembly in solution, thereby changing the size and surface anti-fouling performance of the polymeric micelles. Moreover, star-branched copolymer micelles with a higher branching degree allowed their payload to persist better in blood(half-time prolonged from 7.1, 8.6 to 13.8 h) and for a 1.72-fold higher content at the tumor site. These studies suggest that raising the branching degree of amphiphilic copolymer potentially offers a promising strategy for the design of carriers capable of enhanced circulation and targeting in vivo.