Dataset Information

Integrated analysis of genome-wide DNA methylation, gene expression and protein expression profiles in molecular subtypes of WHO II-IV gliomas.

ABSTRACT: Glioma is the most common malignant primary brain tumor among adults, among which glioblastoma (GBM) exhibits the highest malignancy. Despite current standard chemoradiation, glioma is still invariably fatal. A further insight into the molecular background of glioma is required to improve patient outcomes.Previous studies evaluated molecular genetic differences through comparing different grades of glioma. Here, we integrated DNA methylation, RNA sequencing and protein expression data sets of WHO grade II to IV gliomas, to screen for dysregulated genes in subtypes during malignant progression of glioma.We propose a list of universal genes (UG) as novel glioma biomarkers: 977 up-regulated genes and 114 down-regulated genes, who involved in cell cycle, Wnt receptor signaling pathway and fatty acid metabolic process. Poorer survival was associated significantly with the high expression of 977 up-regulated genes and low expression of 114 down-regulated in UG (P <0.001).To our knowledge, this was the first study that focused on subtypes to detect dysregulated genes that could contribute to malignant progression. Furthermore, the differentially expressed genes profile may lead to the identification of new therapeutic targets for glioma patients.

SUBMITTER: Wang ZL

PROVIDER: S-EPMC4620600 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Integrated analysis of genome-wide DNA methylation, gene expression and protein expression profiles in molecular subtypes of WHO II-IV gliomas.

Wang Zhi-Liang ZL Zhang Chuan-Bao CB Cai Jin-Quan JQ Li Qing-Bin QB Wang Zheng Z Jiang Tao T

Journal of experimental & clinical cancer research : CR 20151026

<h4>Background</h4>Glioma is the most common malignant primary brain tumor among adults, among which glioblastoma (GBM) exhibits the highest malignancy. Despite current standard chemoradiation, glioma is still invariably fatal. A further insight into the molecular background of glioma is required to improve patient outcomes.<h4>Method</h4>Previous studies evaluated molecular genetic differences through comparing different grades of glioma. Here, we integrated DNA methylation, RNA sequencing and ...[more]

PMID: 26502731

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Project description:BackgroundGlioma is the most common of all primary brain tumors with poor prognosis and high mortality. The 2016 World Health Organization classification of the tumors of central nervous system uses molecular parameters in addition to histology to redefine many tumor entities. The new classification scheme divides diffuse gliomas into low-grade glioma (LGG) and glioblastoma (GBM) as per histology. LGGs are further divided into isocitrate dehydrogenase (IDH) wild type or mutant, which is further classified into either oligodendroglioma that harbors 1p/19q codeletion or diffuse astrocytoma that has an intact 1p/19q loci but enriched for ATRX loss and TP53 mutation. GBMs are divided into IDH wild type that corresponds to primary or de novo GBMs and IDH mutant that corresponds to secondary or progressive GBMs. To make the 2016 WHO subtypes of diffuse gliomas more robust, we carried out Prediction Analysis of Microarrays (PAM) to develop DNA methylation signatures for these subtypes.ResultsIn this study, we applied PAM on a training set of diffuse gliomas derived from The Cancer Genome Atlas (TCGA) and identified DNA methylation signatures to classify LGG IDH wild type from LGG IDH mutant, LGG IDH mutant with 1p/19q codeletion from LGG IDH mutant with intact 1p/19q loci and GBM IDH wild type from GBM IDH mutant with an accuracy of 99-100%. The signatures were validated using the test set of diffuse glioma samples derived from TCGA with an accuracy of 96 to 99%. In addition, we also carried out additional validation of all three signatures using independent LGG and GBM cohorts. Further, the methylation signatures identified a fraction of samples as discordant, which were found to have molecular and clinical features typical of the subtype as identified by methylation signatures.ConclusionsThus, we identified methylation signatures that classified different subtypes of diffuse glioma accurately and propose that these signatures could complement 2016 WHO classification scheme of diffuse glioma.

Project description:BACKGROUND:Ovarian cancer is an epithelial malignancy that intrigues people for its poor outcome and lack of efficient treatment, while methylation is an important mechanism that have been recognized in many malignancies. In this study, we attempt to assess abnormally methylated gene markers and pathways in ovarian cancer by integrating three microarray datasets. METHODS:Three datasets including expression (GSE26712 and GSE66957) and methylation (GSE81224) datasets were accessed. GEO2R platform was used to detect abnormally methylated-differentially expressed genes. Protein-protein interaction (PPI) networks were built and analysed for hypermethylated and hypermethylated differentially expressed genes using Cytoscape software and Mcode app. GEPIA and cBioPortal platforms were used to validate the expression of the hub genes and the correlation between their mRNA expressions and methylation levels. Kaplan Meier-plotter platform were used to assess the prognostic significance of the hub genes. RESULTS:Six hundred eighty-one hypomethylated-upregulated genes were detected and involved in Rap1 signaling pathway, biosynthesis of amino acids, endocrine resistance, apoptosis, pathways in cancer. The hub genes were TNF, UBC, SRC, ESR1, CDK1, PECAM1, CXCR4, MUC1, IKBKG. Additionally, 337 hypermethylated-downregulated genes were detected and involved in pathways in cancer, focal adhesion, sphingolipid signaling pathway, EGFR tyrosine kinase inhibitor resistance, cellular senescence. The hub genes were BDNF, CDC42, CD44, PPP2R5C, PTEN, UBB, BMP2, FOXO1, KLHL2. TNF, ESR1, MUC1, CD44, PPP2R5C, PTEN, UBB and FOXO1 showed significant negative correlation between their mRNA expressions and methylation levels. TNF, ESR1 and FOXO1 showed prognostic significance. CONCLUSIONS:Two novel gene networks were found for ovarian cancer. TNF, ESR1, MUC1 and FOXO1 are our candidate genes that might take part in ovarian cancer progression in an epigenetic approach, TNF, ESR1 and FOXO1 may serve as potential markers for ovarian cancer prognosis evaluation.

Dataset Information

Integrated analysis of genome-wide DNA methylation, gene expression and protein expression profiles in molecular subtypes of WHO II-IV gliomas.

Publications

Integrated analysis of genome-wide DNA methylation, gene expression and protein expression profiles in molecular subtypes of WHO II-IV gliomas.

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