Dataset Information

A mesenchymal glioma stem cell profile is related to clinical outcome.

ABSTRACT: Recent studies have demonstrated a relationship between the expression of stem cell-associated genes and relapses in glioblastoma (GBM), suggesting a key role for tumor stem cells in this process. Although there is increasing interest in this field, glioma stem cells (GSCs) are still poorly characterized, their 'stemness' state and factors maintaining these properties remain largely unknown. We performed an expression profiling analysis of pluripotency in gliomaspheres derived from 11 patients. Comparative analysis between GSCs and H1 and H9 human embryonic stem cells as well as H9-derived neural stem cells indicates major variations in gene expression of pluripotency factors Nanog and OCT4, but a stable pattern for SOX2 suggesting its important function in maintaining pluripotency in GSCs. Our results also showed that all GSC lines have the capacity to commit to neural differentiation and express mesenchymal or endothelial differentiation markers. In addition, hierarchical clustering analysis revealed two groups of GSCs reflecting their heterogeneity and identified COL1A1 and IFITM1 as the most discriminating genes. Similar patterns have been observed in tumors from which gliomaspheres have been established. To determine whether this heterogeneity could be clinically relevant, the expression of both genes was further analyzed in an independent cohort of 30 patients with GBM and revealed strong correlation with overall survival. In vitro silencing of COL1A1 and IFTM1 confirmed the effect of these mesenchymal-associated genes on cell invasion and gliomasphere initiation. Our results indicate that COL1A1 and IFITM1 genes could be considered for use in stratifying patients with GBM into subgroups for risk of recurrence at diagnosis, as well as for prognostic and therapeutic evolution.

SUBMITTER: Balbous A

PROVIDER: S-EPMC4038390 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A mesenchymal glioma stem cell profile is related to clinical outcome.

Balbous A A Cortes U U Guilloteau K K Villalva C C Flamant S S Gaillard A A Milin S S Wager M M Sorel N N Guilhot J J Bennaceur-Griscelli A A Turhan A A Chomel J-C JC Karayan-Tapon L L

Oncogenesis 20140317

Recent studies have demonstrated a relationship between the expression of stem cell-associated genes and relapses in glioblastoma (GBM), suggesting a key role for tumor stem cells in this process. Although there is increasing interest in this field, glioma stem cells (GSCs) are still poorly characterized, their 'stemness' state and factors maintaining these properties remain largely unknown. We performed an expression profiling analysis of pluripotency in gliomaspheres derived from 11 patients. ...[more]

PMID: 24637491

Similar Datasets

Project description: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.

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.

Project description:Tumor heterogeneity of high-grade glioma (HGG) is recognized by four clinically relevant subtypes based on core gene signatures. However, molecular signaling in glioma stem cells (GSCs) in individual HGG subtypes is poorly characterized. Previously we identified and characterized two mutually exclusive GSC subtypes with distinct activated signaling pathways and biological phenotypes. One GSC subtype presented with a gene signature resembling Proneural (PN) HGG, whereas the other was similar to Mesenchymal (Mes) HGG. Classical HGG-derived GSCs were sub-classified as either one of these two subtypes. Differential mRNA expression analysis of PN and Mes GSCs identified 5,796 differentially expressed genes, revealing a pronounced correlation with the corresponding PN or Mes HGGs. Mes GSCs displayed more aggressive phenotypes in vitro and as intracranial xenografts in mice. Further, Mes GSCs were markedly resistant to radiation compared with PN GSCs. Expression of ALDH1A3 - one of the most up-regulated Mes representative genes and a universal cancer stem cell marker in non-brain cancers - was associated with self-renewal and a multi-potent stem cell population in Mes but not PN samples. Moreover, inhibition of ALDH1A3 attenuated the growth of Mes but not PN GSCs in vitro. Lastly, radiation treatment of PN GSCs up-regulated Mes-associated markers and down-regulated PN-associated markers, whereas inhibition of ALDH1A3 attenuated an irradiation-induced gain of Mes identity in PN GSCs in vitro. Taken together, our data suggest that two subtypes of GSCs, harboring distinct metabolic signaling pathways, represent intertumoral glioma heterogeneity and highlight previously unidentified roles of ALDH1A3-associated signaling that promotes aberrant proliferation of Mes HGGs and GSCs. Inhibition of ALDH1A3-mediated pathways therefore might provide a promising therapeutic approach for a subset of HGGs with the Mes signature. Here, we describe the gene expression analysis, including pre-processing methods for the data published by Mao and colleagues in PNAS [1], integration of microarray data from this study with The Cancer Genome Atlas (TCGA) glioblastoma data and also with another published study.

Dataset Information

A mesenchymal glioma stem cell profile is related to clinical outcome.

Publications

A mesenchymal glioma stem cell profile is related to clinical outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets