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. 2019 Nov;18(5):3439-3449.
doi: 10.3892/etm.2019.7975. Epub 2019 Sep 5.

Identification of key candidate genes and pathways in glioblastoma by integrated bioinformatical analysis

Lei Li  1 , Xiaohui Liu  2 , Xiaoye Ma  2 , Xianyu Deng  1 , Tao Ji  1 , Pingping Hu  1 , Ronghao Wan  1 , Huijia Qiu  1 , Daming Cui  1   3 , Liang Gao  1   3
Affiliations

Identification of key candidate genes and pathways in glioblastoma by integrated bioinformatical analysis

Lei Li et al. Exp Ther Med. 2019 Nov.

Abstract

Glioblastoma (GBM), characterized by high morbidity and mortality, is one of the most common lethal diseases worldwide. To identify the molecular mechanisms that contribute to the development of GBM, three cohort profile datasets (GSE50161, GSE90598 and GSE104291) were integrated and thoroughly analyzed; these datasets included 57 GBM cases and 22 cases of normal brain tissue. The current study identified differentially expressed genes (DEGs), and analyzed potential candidate genes and pathways. Additionally, a DEGs-associated protein-protein interaction (PPI) network was established for further investigation. Then, the hub genes associated with prognosis were identified using a Kaplan-Meier analysis based on The Cancer Genome Atlas database. Firstly, the current study identified 378 consistent DEGs (240 upregulated and 138 downregulated). Secondly, a cluster analysis of the DEGs was performed based on functions of the DEGs and signaling pathways were analyzed using the enrichment analysis tool on DAVID. Thirdly, 245 DEGs were identified using PPI network analysis. Among them, two co-expression modules comprising of 30 and 27 genes, respectively, and 35 hub genes were identified using Cytoscape MCODE. Finally, Kaplan-Meier analysis of the hub genes revealed that the increased expression of calcium-binding protein 1 (CABP1) was negatively associated with relapse-free survival. To summarize, all enriched Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways may participate in mechanisms underlying GBM occurrence and progression, however further studies are required. CABP1 may be a key gene associated with the biological process of GBM development and may be involved in a crucial mechanism of GBM progression.

Keywords: bioinformatical analysis; calcium-binding protein 1; differentially expressed genes; glioblastoma.

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Figures

Figure 1.
Figure 1.
Identification of DEGs in glioblastomas. A total of 378 commonly altered DEGs were identified from three datasets (GSE50161, GSE90598 and GSE104291) using GEO2R tool. The ‘cross areas’ are common DEGs. A classical t-test was used to identify DEGs; the cut-off criteria were P<0.05 and [log Fold Change]>1. DEGs, differentially expressed genes.
Figure 2.
Figure 2.
Top 10 GO terms of DEGs associated with glioblastomas. Top 10 GO terms of DEGs involved in (A) biological process (B) molecular function and (C) cellular component were obtained by GO analysis. GO, Gene Ontology; DEGs, differentially expressed genes.
Figure 3.
Figure 3.
Top 30 GO terms of DEGs associated with glioblastomas GBM based on their functions. GO, Gene Ontology.
Figure 4.
Figure 4.
Top 30 significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways terms of DEGs associated with glioblastomas using Database for Annotation, Visualization and Integrated Discovery software.
Figure 5.
Figure 5.
DEGs PPI network complex and modular analysis. (A) A total of 245 DEGs (153 upregulated genes and 92 downregulated genes) were filtered into the DEGs PPI network complex using the Search Tool for the Retrieval of Interacting Genes/Proteins database. (B) Module 1 was composed of 30 nodes and 152 edges. (C) Module 2 was composed of 27 nodes and 86 edges. Nodes in red signified upregulation and nodes in green signified downregulation. DEGs, differentially expressed genes; PPI, protein-protein interaction.
Figure 6.
Figure 6.
High CABP1 expression negatively associated with RFS for GBM patients. The RFS of patients with GBM who have low- and high-expression of CABP1 was analyzed with a Kaplan-Meier plot. RFS, relapse-free survival; CABP1, calcium-binding protein 1; GBM, glioblastomas.
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