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. 2021 Apr 29:11:650534.
doi: 10.3389/fonc.2021.650534. eCollection 2021.

High Level of METTL7B Indicates Poor Prognosis of Patients and Is Related to Immunity in Glioma

Yujia Xiong  1 , Mingxuan Li  1 , Jiwei Bai  2 , Yutao Sheng  1 , Yazhuo Zhang  1   2   3   4
Affiliations

High Level of METTL7B Indicates Poor Prognosis of Patients and Is Related to Immunity in Glioma

Yujia Xiong et al. Front Oncol. .

Abstract

Glioma is the most common primary intracranial malignant tumor in adults. Although there have been many efforts on potential targeted therapy of glioma, the patient's prognosis remains dismal. Methyltransferase Like 7B (METTL7B) has been found to affect the development of a variety of tumors. In this study, we collected RNA-seq data of glioma in CGGA and TCGA, analyzed them separately. Then, Kaplan-Meier survival analysis, univariate and multivariate Cox analysis, and receiver operating characteristic curve (ROC curve) analysis were used to evaluate the effect of METTL7B on prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) enrichment analyses were used to identify the function or pathway associated with METTL7B. Moreover, the ESTIMATE algorithm, Cibersort algorithm, Spearman correlation analysis, and TIMER database were used to explore the relationship between METTL7B and immunity. Finally, the role of METTL7B was explored in glioma cells. We found that METTL7B is highly expressed in glioma, and high expression of METTL7B in glioma is associated with poor prognosis. In addition, there were significant differences in immune scores and immune cell infiltration between the two groups with different expression levels of METTL7B. Moreover, METTL7B was also correlated with immune checkpoints. Knockdown of METTL7B revealed that METTL7B promoted the progression of glioma cells. The above results indicate that METTL7B affects the prognosis of patients and is related to tumor immunity, speculating that METTL7B may be a new immune-related target for the treatment of glioma.

Keywords: CGGA TCGA; METTL7B; glioma; immune; prognosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The expression level of METTL7B in glioma. (A) Expression of METTL7B in glioma and normal tissues in GEPIA database. (B) The protein level of METTL7B in glioma and normal tissues based on the Human Protein Atlas. *p < 0.05.
Figure 2
Figure 2
Correlation between the expression of METTL7B and clinical features using CGGA and TCGA database. (A, B) Differential expression of METTL7B was significantly related to the age of the patients, (C, D) WHO stage of glioma, (E, F) histology, (G, H) IDH_mutation. (I, J) The expression level of METTL7B was not correlated with the Gender of patients. *p < 0.05; ****p < 0.0001; ns, not significant.
Figure 3
Figure 3
Survival analysis of METTL7B in CGGA and TCGA patients. (A, B) Kaplan-Meier survival curves in the high and low expressions of METTL7B groups. (C, D) Univariate Cox analysis of METTL7B. (E, F) Multivariate Cox analysis of METTL7B. (G, H) ROC analysis of METTL7B for 1, 3, and 5-year survival.
Figure 4
Figure 4
Differential gene enrichment analysis between different METTL7B groups. (A, B) Top 10 GO terms, involving BP, CC, and MF. (C, D) Top 30 KEGG pathways. (E, F) GSEA enrichment analysis revealed potential associations between METTL7B and several immune-associated pathways.
Figure 5
Figure 5
Relationship between ESTIMATE score and METTL7B expression level in CGGA and TCGA patients. (A, B) Immunescore, (C, D) stromalscore, and (E, F) ESTIMATEscore were higher in the group with higher METTL7B expression. ****p < 0.0001.
Figure 6
Figure 6
Kaplan-Meier survival curves of ESTIMATE score. High levels of (A, B) immunescore, (C, D) stromalscore, and (E, F) ESTIMATEscore correlated with poor prognosis.
Figure 7
Figure 7
The circle diagram showed that METTL7B was positively correlated with multiple immune checkpoints, PD1, PDL1, CTLA4, LAG3, and TIM3 in glioma patients. (A) CGGA. (B) TCGA.
Figure 8
Figure 8
Proportions of the 22 types of tumor-infiltrate immune cells in different METTL7B groups in (A) CGGA and (B) TCGA. Correlation analysis between METTL7B and 22 kinds of immune cells in glioma. METTL7B was positively associated with (C) Macrophages M1, (D) T cells regulatory, (E) NK cells activated, (F) Mast cells activated in CGGA. (G) Macrophages M1, (H) T cells CD8, (I) Macrophages M0, (J) Neutrophils infiltration were positively correlated with METTL7B expression in TCGA.
Figure 9
Figure 9
The relationship between METTL7B expression level, tumor purity, and immune cell infiltration was explored using the TIMER database. METTL7B was significantly correlated with immune cell infiltration in (A) GBM and (B) LGG patients. Kaplan-Meier survival analysis of several immune cells in (C) GBM and (D) LGG patients.
Figure 10
Figure 10
(A) qRT-PCR revealed that the METTL7B mRNA level was significantly suppressed using METTL7B siRNAs. (B) Western blotting indicated that the expression of METTL7B was decreased after treated with METTL7B siRNAs. (C) CCK8 assay showed that the proliferation ability of glioma cells was significantly decreased after knockdown of METTL7B. (D–F) Transwell assay revealed that knockdown of METTL7B inhibited the migration and invasion ability of glioma cells. Magnification, 200X. **p < 0.01; ***p < 0.001.
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