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. 2017 Nov 15:10:5463-5470.
doi: 10.2147/OTT.S139243. eCollection 2017.

Identification of COX5B as a novel biomarker in high-grade glioma patients

Tieyi Hu  1 , Jiazhuang Xi  2
Affiliations

Identification of COX5B as a novel biomarker in high-grade glioma patients

Tieyi Hu et al. Onco Targets Ther. .

Abstract

Background: Malignant glioma is the second leading cause of cancer-related death worldwide, and is known to exhibit a high degree of heterogeneity in its deregulation of different oncogenic pathways. The molecular subclasses of human glioma are not well known. Thus, it is crucial to identify vital oncogenic pathways in glioma with significant relationships to patient survival.

Methods: In this study, we devised a bioinformatics strategy to map patterns of oncogenic pathway activation in glioma, from the Gene Expression Omnibus (GEO). Bioinformatics analysis revealed that 749 genes were differentially expressed and classified into different glioma grades.

Results: Using gene expression signatures, we identified three oncogenic pathways (MAPK signaling pathway, Wnt signaling pathway, and ErbB signaling pathway) deregulated in the majority of human glioma. Following gene microarray analysis, the gene expression profile in the differential grade glioma was further validated by bioinformatic analyses, with coexpression network construction. Furthermore, we found that cytochrome c oxidase subunit Vb (COX5B), the terminal enzyme of the electron transport chain, was the central gene in a coexpression network that transfers electrons from reduced cytochrome c to oxygen and, in the process, generates an electrochemical gradient across the mitochondrial inner membrane. The expression level of COX5B was then detected in 87 glioma tissues as well as adjacent normal tissues using immunohistochemistry. We found that COX5B was significantly upregulated in 67 of 87 (77.0%) glioma and glioblastoma tissues, compared with adjacent tissue (p<0.01). Furthermore, statistical analysis showed the COX5B expression level was significantly associated with clinical stage and lymph node status, while there were no correlations between COX5B expression and age or tumor size.

Conclusion: These data indicate that COX5B may be implicated in glioma pathogenesis and as a biomarker for identification of the pathological grade of glioma.

Keywords: COX5B; bioinformatics; biomarker; glioblastoma.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Differently expressed gene in grade I to IV glioma. (A) 3726 genes were deregulated in high-grade glioma under the condition of “Q <0.05 and fold change >1.2”. (B) 749 genes were deregulated in high-grade glioma under the condition of “Q <0.001 and fold change >2”. (C) Top 20 expression signature genes.
Figure 2
Figure 2
Cluster analysis of differently expressed gene, (A) the top 20 significant cluster profiles. (B) Of these clusters, number 80 comprised genes that gradually expressed different levels at different points of time.
Figure 3
Figure 3
Gene Ontology and pathway analysis. (A) Top 15 highly enriched GO terms. (B) Top 15 highest degree pathways.
Figure 3
Figure 3
Gene Ontology and pathway analysis. (A) Top 15 highly enriched GO terms. (B) Top 15 highest degree pathways.
Figure 4
Figure 4
Pathway relation network and gene coexpression network. (A) Fifty two significantly changed pathways relation network. (B) All differently expressed genes in a coexpression network. (C) The COX5B gene localizes at the center of subnetwork in the coexpression network, which directly regulates 15 adjacent genes that network according to their degrees. Node size represents the degree of centrality.
Figure 5
Figure 5
COX5B expression is overexpressed in different-grade II to IV glioma tissue. Magnification 200×.
See this image and copyright information in PMC

References

    1. Sancho-Martinez I, Nivet E, Xia Y, et al. Establishment of human iPSC-based models for the study and targeting of glioma initiating cells. Nat Commun. 2016;7:10743. - PMC - PubMed
    1. Tate MC, Herbet G, Moritz-Gasser S, Tate JE, Duffau H. Probabilistic map of critical functional regions of the human cerebral cortex: Broca’s area revisited. Brain. 2014;137(Pt 10):2773–2782. - PubMed
    1. Caretti V, Sewing AC, Lagerweij T, et al. Human pontine glioma cells can induce murine tumors. Acta Neuropathol. 2014;127(6):897–909. - PMC - PubMed
    1. Tabu K, Sasai K, Kimura T, et al. Promoter hypomethylation regulates CD133 expression in human gliomas. Cell Res. 2008;18(10):1037–1046. - PubMed
    1. Urgesi C, Aglioti SM, Skrap M, Fabbro F. The spiritual brain: selective cortical lesions modulate human self-transcendence. Neuron. 2010;65(3):309–319. - PubMed