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P04.38 Orai2 related transcriptome profile and clinical outcome in classical and mesenchymal subtype of glioblastoma

ABSTRACT: Abstract Background Ca2+ release-activated Ca2+ channels (CRAC) is the main Ca2+ entry pathway regulating intracellular Ca2+ concentration in a variety of cancer types. Orai2 is the main pore-forming subunit of CRAC channels in central neurons; To characterize the role of Orai2 in glioma, we investigated its related biological process, molecular function and KEGG pathways at transcriptome level and its clinical prognostic value. Material and Methods Through TCGA, French, Sun and GEO (GSE23806) dataset, we systematically reviewed a total of 1231 cases with RNA-seq data and analyzed the functional annotation of Orai2 by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis. Univariate and multivariate survival analysis were performed in 823 patients with survival data. Results We found Orai2 was significantly upregulated in glioblastoma. Survival analysis suggested that higher Orai2 expression was independently associated with worse prognosis of patients with classical and mesenchymal subtype of glioblastoma. According to TCGA transcriptional classification scheme, Orai2 expression was higher in tumors of classical and mesenchymal subtype than other subtypes, and shown significantly correlation with classical and mesenchymal related genes. GO KEGG Pathway analysis revealed that genes significantly correlated with Orai2 were involved in essential functions associated with stemness, apoptosis and EMT process. Through screening transcriptomic data, we found a strong correlation between Orai2 and apoptosis, stemness and Epithelial to mesenchymal(?like) transition (EMT) related genes including Nestin, SOX2, NOTCH1, TP53, Caspase 3, Cytochrome C, CDH2, ZEB1, VIM. Conclusion Orai2 is a prognostic factor that is distinctly activated in the classical and mesenchymal subtype of glioblastoma and that promotes glioma GSCs selfrenewal, apoptosis process and mesenchymal transition via the JNK pathway. These findings suggested Orai2 as a candidate for a therapeutic target for classical and mesenchymal subtype of GBM.

SUBMITTER: YUAN F

PROVIDER: S-EPMC6144634 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Project description:BackgroundIncreasing evidence has indicated that the nuclear receptor subfamily 3 group C member 2 (NR3C2) may be associated with tumorigenesis and patient prognosis for certain types of tumors. However, the clinical significance of NR3C2 is unclear in invasive breast carcinoma (BRCA).MethodsWe used bioinformatics to broadly investigate and obtain a deeper understanding of the prognostic significance between NR3C2 and BRCA. RNA-sequencing data and clinical information of patients with BRCA from the Cancer Genome Atlas database were collected for subsequent analysis. The diagnostic efficacy of NR3C2 was evaluated by calculating the receiver operating characteristic curve. The prognostic value of NR3C2 was evaluated by Kaplan-Meier analysis and Cox regression analysis for patients with BRCA. Moreover, the OSbrca database was used to validate NR3C2 as a prognostic biomarker for BRCA. Gene set enrichment analysis (GSEA) and tumor immune infiltration analysis were conducted to explore the molecular mechanism of NR3C2 in BRCA.ResultsThe expression level of NR3C2 in BRCA tissues decreased compared to that in normal breast tissues (P < 0.001). NR3C2 presented good diagnostic efficacy (AUC = 0.908). Moreover, the expression of NR3C2 was verified using the Oncomine database. High expression of NR3C2 was statistically associated with prolonged overall survival (HR = 0.65, 95% CI: 0.47-0.91, and P = 0.012), progression-free interval (HR = 0.68, 95% CI: 0.49-0.95, and P = 0.024), and disease-specific survival (HR = 0.57, 95% CI: 0.36-0.89, and P = 0.015) for patients with BRCA. Besides, the prognostic value of NR3C2 was verified by the OSbrca database. GSEA results suggested that enriched pathways included neuroactive ligand-receptor interaction, focal adhesion, and ECM-receptor interaction. NR3C2 expression was moderately correlated with mast cells and some T cell subsets in BRCA.ConclusionNR3C2 is a potential prognostic biomarker that could help clinicians develop more appropriate treatment plans for individual patients with BRCA.

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P04.38 Orai2 related transcriptome profile and clinical outcome in classical and mesenchymal subtype of glioblastoma

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