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. 2022 Feb 2:12:842973.
doi: 10.3389/fonc.2022.842973. eCollection 2022.

Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma

Xuelei Lin  1   2 , Hongwei Liu  1   2 , Hongyu Zhao  1   2 , Shunjin Xia  1   2 , Yueshuo Li  1 , Chaoqian Wang  1   2 , Qi Huang  1   2 , Siyi Wanggou  1   2 , Xuejun Li  1   2
Affiliations

Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma

Xuelei Lin et al. Front Oncol. .

Abstract

Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. Alteration in MAN2B1 has been proved to be accountable for several diseases. However, the relationship between MAN2B1 and glioma malignancy remains unclear. In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. We found that MAN2B1 was elevated in glioma and was correlated with malignant clinical and molecular features. Upregulated expression of MAN2B1 is prognostic for poor outcomes in glioma patients. Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. Functional enrichment analysis showed that MAN2B1 was involved in immune and inflammation processes. Moreover, MAN2B1 expression was strongly correlated with M2 macrophages and weakly correlated with M1 macrophages. Further analysis confirmed that MAN2B1 was closely associated with the markers of M2 macrophages and tumor-associated macrophages. Taken together, MAN2B1 is a potential prognostic biomarker in glioma and associates with immune infiltration.

Keywords: MAN2B1; glioma; immune infiltrates cells; prognosis; tumor-associated macrophage.

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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
Workflow to show our data collecting and analysis processing.
Figure 2
Figure 2
The correlation between MAN2B1 and clinicopathological characteristics in glioma. (A) The MAN2B1 mRNA expression in 31 TCGA cancers. (B, F) Distinct MAN2B1 expression between different WHO grades in TCGA and CGGA. (C, G) Different MAN2B1 expression levels between GBM and astrocytoma, oligoastrocytoma, oligodendroglioma, respectively. (D, H) Higher MAN2B1 expression in the IDH wild type compared with IDH mutant gliomas. (E, I) The mRNA level of MAN2B1 was higher in IDH wild type gliomas compared with IDH mutant gliomas in each grade. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. Ns, not statistically significant.
Figure 3
Figure 3
The expression of MAN2B1 was obviously upregulated in glioma tissue. (A) RT-qPCR analysis of the different MAN2B1 expression in gliomas and adjacent normal tissues. (B) RT-qPCR analysis of the different MAN2B1 expression in glioma cell lines and normal cell lines. (C) The expression of MAN2B1 protein in glioma cell lines and normal astrocyte HEB cell line by WB. (D) RT-qPCR analysis of the different MAN2B1 protein in GBM and LGG tissues. (E) IHC staining of MAN2B1 protein expression in GBM and LGG. (F) The average optical density of the positive cells in GBM and LGG tissues. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Scale bar, 20µm.
Figure 4
Figure 4
The correlation between clinical outcome and MAN2B1 expression. (A) The high mRNA expression of MAN2B1 is associated with poor outcomes in GBM, LGG, CESC, and KIRC. (B, F) Poor survival in gliomas with high MAN2B1 expression in both TCGA and CGGA databases. (C–I) The prognostic value of MAN2B1 expression in each WHO grade. (J) Forest plot shows that upregulated MAN2B1 expression is independent hazard factor for glioma. OS, overall survival; DFS, disease-free survival; HR, hazard ratio; CI, confidence interval. *p < 0.05, **p < 0.01, ***p < 0.001.
Figure 5
Figure 5
Different genomic profiles associated with MAN2B1 expression. (A, B) Distinct somatic mutations were found in gliomas with low MAN2B1 expression (A) and in gliomas with high MAN2B1 expression (B).
Figure 6
Figure 6
Functional enrichment analysis. (A) The DEGs between the high and low MAN2B1 expression groups in the volcano plot. (B, C) Enriched GO terms in the BP category showing that the MAN2B1 gene was mostly enriched in the inflammatory response and immune response in TCGA and CGGA datasets. (D, E) Enriched KEGG terms showing that the MAN2B1 gene was associated with inflammatory response and immune response in TCGA and CGGA datasets.
Figure 7
Figure 7
MAN2B1 related immune response and inflammatory activities in gliomas. (A, B) Heatmaps showed that the 10 hallmark gene sets were positively correlated with MAN2B1 expression in TCGA and CGGA datasets. (C) Correlation between 21 kinds of immune infiltrating cells and MAN2B1 expression.
Figure 8
Figure 8
Correlation of MAN2B1 expression with macrophage polarization in glioma. Scatterplots of the correlations between MAN2B1 expression and gene markers of M1 macrophages (NOS2 and TNF) (A), M2 macrophages (CD163 and TGFBI) (B), and TAMs (CCL2, and IL10) (C).
See this image and copyright information in PMC

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