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Identification of differential splicing genes in gliomas using exon expression profiling.

Yu F, Fu WM - Mol Med Rep (2014)

Bottom Line: A total of 300 DEGs were identified to be shared by GBM and OD, including 97 upregulated and 203 downregulated DEGs.Furthermore, screening with a defined threshold identified 6 genes that were highly expressed in GBM, including AFF2, CACNA2D3 and ARPP21, while the 6 highly expressed genes in OD notably included CNTN2.The TP53 and HIST1H3A genes were the hub nodes in the PPI network of DEGs from GBM, while CNTN2 was linked to the highest degree in the OD PPI network.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.

ABSTRACT
Diffuse gliomas are the most common type of malignant primary brain tumor, and their initiation and/or progression are often associated with alternative splicing. They produce an enormous economic burden on society and greatly impair the quality of life of those affected. The aim of the current study was to explore the differentially expressed genes (DEGs) observed in glioblastoma (GBM) and oligodendroglioma (OD) at the splicing level, and to analyze their functions in order to identify the underlying molecular mechanisms of gliomas. The exon‑level expression profile data GSE9385 was downloaded from the Gene Expression Omnibus database, and included 26 GBM samples, 22 OD samples and 6 control brain samples. The differentially expressed exon‑level probes were analyzed using the microarray detection of alternative splicing algorithm combined with the splicing index method, and the corresponding DEGs were identified. Next, a Gene Ontology enrichment analysis of the DEGs was performed. Additionally, the protein‑protein interaction (PPI) networks were constructed based on the depth‑first search algorithm. A total of 300 DEGs were identified to be shared by GBM and OD, including 97 upregulated and 203 downregulated DEGs. Furthermore, screening with a defined threshold identified 6 genes that were highly expressed in GBM, including AFF2, CACNA2D3 and ARPP21, while the 6 highly expressed genes in OD notably included CNTN2. The TP53 and HIST1H3A genes were the hub nodes in the PPI network of DEGs from GBM, while CNTN2 was linked to the highest degree in the OD PPI network. The present study provides a comprehensive bioinformatics analysis of DEGs in GBM and OD, which may provide a basis for understanding the initiation and/or progression of glioma development.

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Related in: MedlinePlus

Identification of DEGs using the SI method and MIDAS algorithm. (A) DEGs between GBM/OD samples, GBM/normal samples and OD/normal samples. (B) A total of 617 and 498 differentially expressed exon-level genes were identified in GBM and OD compared with the control, respectively. A total of 97 upregulated and 203 downregulated genes were identified in both GBM and OD. DEG, differentially expressed gene; SI, splicing index; MIDAS, microarray detection of alternative splicing; GBM, glioblastoma; OD, oligodendroglioma; CTR, control.
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f2-mmr-11-02-0843: Identification of DEGs using the SI method and MIDAS algorithm. (A) DEGs between GBM/OD samples, GBM/normal samples and OD/normal samples. (B) A total of 617 and 498 differentially expressed exon-level genes were identified in GBM and OD compared with the control, respectively. A total of 97 upregulated and 203 downregulated genes were identified in both GBM and OD. DEG, differentially expressed gene; SI, splicing index; MIDAS, microarray detection of alternative splicing; GBM, glioblastoma; OD, oligodendroglioma; CTR, control.

Mentions: The expression values of these 982 DEGs were hierarchically clustered by the Hclust package of R software (Fig. 1). Compared with normal brain tissue, 617 and 498 DEGs were identified in GBM and OD, respectively (Fig. 2A). A total of 97 upregulated and 203 downregulated DEGs were identified to be present in both GBM and OD (Fig. 2B), and 236 DEGs were obtained between GBM and OD, 94 of which were upregulated and 142 downregulated in GBM (Fig. 2A).


Identification of differential splicing genes in gliomas using exon expression profiling.

Yu F, Fu WM - Mol Med Rep (2014)

Identification of DEGs using the SI method and MIDAS algorithm. (A) DEGs between GBM/OD samples, GBM/normal samples and OD/normal samples. (B) A total of 617 and 498 differentially expressed exon-level genes were identified in GBM and OD compared with the control, respectively. A total of 97 upregulated and 203 downregulated genes were identified in both GBM and OD. DEG, differentially expressed gene; SI, splicing index; MIDAS, microarray detection of alternative splicing; GBM, glioblastoma; OD, oligodendroglioma; CTR, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262513&req=5

f2-mmr-11-02-0843: Identification of DEGs using the SI method and MIDAS algorithm. (A) DEGs between GBM/OD samples, GBM/normal samples and OD/normal samples. (B) A total of 617 and 498 differentially expressed exon-level genes were identified in GBM and OD compared with the control, respectively. A total of 97 upregulated and 203 downregulated genes were identified in both GBM and OD. DEG, differentially expressed gene; SI, splicing index; MIDAS, microarray detection of alternative splicing; GBM, glioblastoma; OD, oligodendroglioma; CTR, control.
Mentions: The expression values of these 982 DEGs were hierarchically clustered by the Hclust package of R software (Fig. 1). Compared with normal brain tissue, 617 and 498 DEGs were identified in GBM and OD, respectively (Fig. 2A). A total of 97 upregulated and 203 downregulated DEGs were identified to be present in both GBM and OD (Fig. 2B), and 236 DEGs were obtained between GBM and OD, 94 of which were upregulated and 142 downregulated in GBM (Fig. 2A).

Bottom Line: A total of 300 DEGs were identified to be shared by GBM and OD, including 97 upregulated and 203 downregulated DEGs.Furthermore, screening with a defined threshold identified 6 genes that were highly expressed in GBM, including AFF2, CACNA2D3 and ARPP21, while the 6 highly expressed genes in OD notably included CNTN2.The TP53 and HIST1H3A genes were the hub nodes in the PPI network of DEGs from GBM, while CNTN2 was linked to the highest degree in the OD PPI network.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.

ABSTRACT
Diffuse gliomas are the most common type of malignant primary brain tumor, and their initiation and/or progression are often associated with alternative splicing. They produce an enormous economic burden on society and greatly impair the quality of life of those affected. The aim of the current study was to explore the differentially expressed genes (DEGs) observed in glioblastoma (GBM) and oligodendroglioma (OD) at the splicing level, and to analyze their functions in order to identify the underlying molecular mechanisms of gliomas. The exon‑level expression profile data GSE9385 was downloaded from the Gene Expression Omnibus database, and included 26 GBM samples, 22 OD samples and 6 control brain samples. The differentially expressed exon‑level probes were analyzed using the microarray detection of alternative splicing algorithm combined with the splicing index method, and the corresponding DEGs were identified. Next, a Gene Ontology enrichment analysis of the DEGs was performed. Additionally, the protein‑protein interaction (PPI) networks were constructed based on the depth‑first search algorithm. A total of 300 DEGs were identified to be shared by GBM and OD, including 97 upregulated and 203 downregulated DEGs. Furthermore, screening with a defined threshold identified 6 genes that were highly expressed in GBM, including AFF2, CACNA2D3 and ARPP21, while the 6 highly expressed genes in OD notably included CNTN2. The TP53 and HIST1H3A genes were the hub nodes in the PPI network of DEGs from GBM, while CNTN2 was linked to the highest degree in the OD PPI network. The present study provides a comprehensive bioinformatics analysis of DEGs in GBM and OD, which may provide a basis for understanding the initiation and/or progression of glioma development.

Show MeSH
Related in: MedlinePlus