Dataset Information

Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma.

ABSTRACT:

Background

Increasing evidence has shown that long non-coding RNAs (lncRNAs) are important prognostic biomarkers and epigenetic regulators with critical roles in cancer initiation and progression. However, the expression and clinical prognostic value of antisense lncRNAs in diffuse glioma patients remain unknown.

Methods

Here, we profiled differentially expressed antisense lncRNAs in glioma using RNA sequencing data from Chinese Glioma Genome Atlas database. Cox regression was performed to evaluate the prognostic value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were used for functional analysis of antisense LncRNAs.

Results

Expression profiling identified 169 aberrantly expressed antisense lncRNAs between lower grade glioma (LGG) (grade II and III) and glioblastoma multiforme (GBM), 113 antisense lncRNAs between LGG IDH-wt and IDH-mut samples, and 70 antisense lncRNAs between GBM IDH-wt and IDH-mut samples, respectively. Among them, three antisense lncRNAs (WDFY3-AS2, MCM3AP-AS1 and LBX2-AS1) were significantly associated with prognosis and malignant progression of patients. WDFY3-AS2, the top one of downregulated antisense lncRNAs in GBM with fold change of 0.441 (P?ConclusionOur findings provided convincing evidence that WDFY3-AS2 is a novel valuable prognostic biomarker for diffuse glioma.

SUBMITTER: Wu F

PROVIDER: S-EPMC6064140 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma.

Wu Fan F Zhao Zheng Z Chai Ruichao R Liu Yuqing Y Wang Kuanyu K Wang Zhiliang Z Li Guanzhang G Huang Ruoyu R Jiang Haoyu H Zhang Kenan K

Cancer cell international 20180728

<h4>Background</h4>Increasing evidence has shown that long non-coding RNAs (lncRNAs) are important prognostic biomarkers and epigenetic regulators with critical roles in cancer initiation and progression. However, the expression and clinical prognostic value of antisense lncRNAs in diffuse glioma patients remain unknown.<h4>Methods</h4>Here, we profiled differentially expressed antisense lncRNAs in glioma using RNA sequencing data from Chinese Glioma Genome Atlas database. Cox regression was per ...[more]

PMID: 30069164

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Project description:Malignant gliomas are the most common type of primary malignancy of the central nervous system with a poor prognosis. Stanniocalcin 1 (STC1) is closely associated with tumor genesis and development. However, its role in the development and progression of glioma is poorly understood. In silico analysis, The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Rembrandt and GSE16011 datasets were used to assess the expression levels of STC1 in non-tumor brain tissues and gliomas. Moreover, reverse transcription-quantitative PCR and immunohistochemistry were used to detect STC1 expression in tumor tissues collected in the Department of Neurosurgery of Shenzhen People's Hospital (Shenzhen, China). The association between STC1 expression and different molecular pathological features was analyzed in four public datasets, as well as via Kaplan-Meier analysis. Furthermore, normalized mRNA expression in TCGA was used to perform Gene Ontology analysis. It was revealed that STC1 expression was significantly elevated in glioma tissues compared with the non-tumor brain tissues, both in silico analysis and via cohort validation. According to TCGA, CGGA, Rembrandt and GSE16011 datasets, it was identified that STC1 expression was increased in high grade glioma compared with low grade glioma. In addition, the results indicated STC1 expression was enriched in the isocitrate dehydrogenase (IDH) wild-type and mesenchymal subtype in TCGA, GSE16011 and Rembrandt datasets. Moreover, it was demonstrated that patients with higher STC1 expression exhibited shorter overall survival times compared with those with lower STC1 expression using Kaplan-Meier analysis, according to both the public datasets and validation cohort. Furthermore, the results of the Gene Ontology analysis demonstrated that STC1 was primarily involved in the reorganization of extracellular matrix and was significantly correlated with invasive-related proteins. Therefore, the present results indicate that STC1 was upregulated in glioma tissues and may represent a prognostic biomarker in patients with glioma.

Project description:Objective: Brain tumors (gliomas) contain large populations of infiltrating macrophages and recruited microglia, which in experimental murine glioma models promote tumor formation and progression. Among the barriers to understanding the contributions of these stromal elements to high-grade glioma (glioblastoma; GBM) biology is the relative paucity of tools to characterize infiltrating macrophages and resident microglia. In this study, we leveraged multiple RNA analysis platforms to identify new monocyte markers relevant to GBM patient outcome. Methods: High-confidence lists of mouse resident microglia- and bone marrow-derived macrophage-specific transcripts were generated using converging RNA-seq and microarray technologies and validated using qRT-PCR and flow cytometry. Expression of select cell surface markers was analyzed in brain-infiltrating macrophages and resident microglia in an induced GBM mouse model, while allogeneic bone marrow transplantation was performed to trace the origins of infiltrating and resident macrophages. Glioma tissue microarrays were examined by immunohistochemistry, and the Gene Expression Omnibus (GEO) database was queried to determine the prognostic value of identified microglia biomarkers in human GBM. Results: We generated a unique catalog of differentially-expressed bone marrow-derived monocyte and resident microglia transcripts, and demonstrated that brain-infiltrating macrophages acquire F11R expression in GBM and following bone-marrow transplantation. Moreover, mononuclear cell F11R expression positively correlates with human high-grade glioma and additionally serves as a biomarker for GBM patient survival, regardless of GBM molecular subtype. Significance: These studies establish F11R as a novel monocyte prognostic marker for GBM critical for defining a subpopulation of stromal cells for future potential therapeutic intervention. Total RNA was isolated from three independently-generated sets of flow sorted bone marrow monocytes (CD11b+ CD45high CD115+ Ly6G- cells) and brainstem microglia (CD11b+ CD45low CD115low Ly6G- cells) for Illumina RNA-Seq, and two additional pools were subsequently generated and submitted for Affymetrix Mouse Exon 1.0ST microarray. Two of the RNA-Seq samples were additionally analyzed by the microarray, for a total of 6 samples (3 monocyte, 3 microglia) in each platform. Data outputs were analyzed by two analysis methods each (RNA-Seq data: ALEXA-Seq and Cufflinks; microarray data: Partek and Aroma). All four lists were merged into a new high-confidence gene list of transcripts that were significantly differentially expressed (DE) in three out of the four analyses. In this dataset, we includeRNA-Seq data obtained from flow sorted mouse bone marrow monocytes and brainstem microglia.

Dataset Information

Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma.

Background

Methods

Results

Publications

Expression profile analysis of antisense long non-coding RNA identifies WDFY3-AS2 as a prognostic biomarker in diffuse glioma.

Similar Datasets

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