Screening recurrent glioblastoma-related genes and analyzing their gene expressions in association with clinicopathological parameters and prognosis

doi:10.19401/j.cnki.1007-3639.2022.01.002

Abstract

Abstract:

Background and purpose: Glioma is the most common and malignant primary brain tumor in the central nervous system (CNS). Glioblastoma is highly malignant and aggressive, and the prognosis of patients with recurrent glioblastoma is very poor. This study aimed to screen the genes related to the recurrent glioblastoma, and analyze the relationship between their expressions, clinicopathological parameters and prognosis in glioma. Methods: By mining the relevant datasets of the primary and recurrent cases of glioblastoma in the GEO database, the differentially expressed gene (DEG) in the samples of primary and recurrent glioblastomas were screened and analyzed. All DEGs analyses were carried out in ontology function and pathway enrichment. Protein-protein interaction (PPI) network was constructed and used for screening Hub gene. Key genes were intersected by PPI network and Venn diagram, and the Gene Expression Profiling Interactive Analysis (GEPIA) and Chinese Glioma Genome Atlas (CGGA) database were analyzed for association of key gene expressions and survival status. Key genes were furtherly analyzed to determine the relationship between their expressions and clinicopathological parameters of glioma. Results: There were 40 DEG screened in the dataset GSE62153, including 34 up-regulated genes and 6 down-regulated genes. There were 19 DEG screened in the dataset GSE58399, including 16 up-regulated genes and 3 down-regulated genes. Go functional analyses showed that the DEG of GSE62153 were mainly involved in 11 physiological processes, such as central nervous system development, myelin sheath, actin binding, central nervous system myelination. The DEG of GSE58399 were mainly enriched in the positive regulation of epithelial cell migration. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment showed that the datasets GSE62153 and GSE58399 were both enriched in histidine metabolism. By using the STRING database, the core of PPI network was constructed with 20 protein molecules. A total of 10 hub genes were screened, including MOBP, OPALIN, ERMN, PLP1, MOG, CLDN11, ASPA, TMEM125, KLK6 and NKX6-2 gene. The key genes for recurrent glioblastoma were ERMN, MOG and MOBP gene. Based on analyses using The Cancer Genome Atlas (TCGA) and CGGA databases, the prognosis of patients with high expressions of ERMN, MOG and MOBP was favorable compared with the low expression group. The expression levels of key genes in glioblastoma were lower compared with the control tissues (P<0.001). There were significant differences in the expressions of ERMN, MOG and MOBP gene among different World Health Organization (WHO) grades (WHO Ⅱ, Ⅲ and Ⅳ) (P<0.001). As the grade of glioblastoma increased, the expressions of ERMN, MOG and MOBP were decreased gradually. The expressions of ERMN, MOG and MOBP gene were correlated with WHO classification, isocitrate dehydrogenase (IDH) status and clinicopathological characteristics (P<0.001). The expression of MOBP gene was correlated with age (P<0.001) and MGMT methylation status (P=0.022). Conclusion: ERMN, MOG and MOBP gene may function as tumor suppressor genes and participate in the recurrence of glioblastoma. The histidine metabolism pathway may be related to the sensitivity of methotrexate treatment.

Key words: Glioma, Bioinformatics, Survival, Recurrence, Histidine metabolism

CLC Number:

R739.41

LIN Yi, WANG Ce, KANG Xun, KANG Zhuang, CHEN Feng, JIANG Bo, LI Wenbin. Screening recurrent glioblastoma-related genes and analyzing their gene expressions in association with clinicopathological parameters and prognosis[J]. China Oncology, 2022, 32(1): 13-23.

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Databases	Website
STRING	https://string-db.org/
GEPIA	http://gepia.cancer-pku.cn/
CGGA	http://www.cbioportal.org

Category	Term	Description	Count n (%)	P value	Gene
BP	GO: 0007417	Central nervous system development	4 (12.01)	0.001	SH3GL3, MOG, SH3GL2, KLK6
CC	GO: 0043209	Myelin sheath	4 (12.10)	0.002	CLDN11, MOBP, PLP1, ERMN
MF	GO: 0003779	Actin binding	4 (12.10)	0.011	MYBPC1, MOBP, DAAM2, PHACTR3
BP	GO: 0022010	Central nervous system myelination	2 (6.06)	0.012	NKX6-2, PLP1
BP	GO: 0008366	Axon ensheathment	2 (6.06)	0.012	CLDN11, PLP1
MF	GO: 0008599	Protein phosphatase type 1 regulator activity	2 (6.06)	0.016	PPP1R1B, PHACTR3
MF	GO: 0019911	Structural constituent of myelin sheath	2 (6.06)	0.016	MOBP, PLP1
BP	GO: 0019371	Cyclooxygenase pathway	2 (6.06)	0.018	AKR1C3, PTGDS
MF	GO: 0031432	Titin binding	2 (6.06)	0.023	MYBPC1, CAPN3
BP	GO: 0006796	Phosphate-containing compound metabolic process	2 (6.06)	0.032	ENPP2, LHPP
MF	GO: 0042802	Identical protein binding	5 (15.15)	0.034	CLDN11, SH3GL3, HSPB8, SH3GL2, ETNPPL

Category	Term	Description	Count n (%)	P value	Gene
BP	GO: 0010634	Positive regulation of epithelial cell migration	2 (12.5)	0.027	DOCK5, ENPP2
KEGG	hsa00340	Histidine metabolism	2 (12.5)	0.016	ASPA, CNDP1