METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Abstract

Methyltransferase-like 7B (METTL7B) is a member of the methyltransferase-like protein family that plays an important role in the development and progression of tumors. However, its prognostic value and the correlation of METTL7B expression and tumor immunity in some cancers remain unclear. By analyzing online data, we found that METTL7B is abnormally overexpressed in multiple human tumors and plays an important role in the overall survival (OS) of patients with 8 cancer types and disease-free survival (DFS) of patients with 5 cancer types. Remarkably, METTL7B expression was positively correlated with the OS and DFS of patients with lower-grade glioma (LGG). In addition, a positive correlation between METTL7B expression and immune cell infiltration in LGG was observed. Moreover, we identified a strong correlation between METTL7B expression and immune checkpoint gene expression in kidney chromophobe (KICH), LGG and pheochromocytoma and paraganglioma (PCPG). Furthermore, METTL7B was involved in the extracellular matrix (ECM) and immune-related pathways in LGGs. Finally, in vitro experiments showed that knockdown of METTL7B inhibited the growth, migration, invasion and the epithelial-mesenchymal transition (EMT) of LGG cells. METTL7B expression potentially represents a novel prognostic biomarker due to its significant association with immune cell infiltration in LGG.

Keywords: Epithelial–mesenchymal transition (EMT); Glioma; Immune cell infiltration; Methyltransferase-like 7B; Pan-cancer analysis; Prognostic markers.

Fig. 1

Flow chart of the research methodology and design

Fig. 2

The expression levels of METTL7B in the human pan-cancer dataset. A METTL7B expression in 31 normal human tissues in the GTEx data set. B METTL7B expression in 21 tumor cells in the CCLE dataset. C Differential expression of METTL7B in normal tissues and cancers in TCGA datasets. D METTL7B was significantly upregulated in 22 cancer types from the TCGA and GTEx databases (*P < 0.05, **P < 0.01, and ***P < 0.001)

Fig. 3

Survival analyses based on differences in METTL7B expression in patients with different cancers. A–H OS, overall survival; I–M DFS, disease-free survival

Fig. 4

METTL7B expression is positively correlated with immune cell infiltration in cancers. A BRCA. B LGG. C PRAD

Fig. 5

Correlations of the immune score, stromal score, and ESTIMATE scores with METTL7B expression in the top three cancers. A SARC. B LGG. C PARD

Fig. 6

Correlation between METTL7B expression and immune checkpoint molecule expression

Fig. 7

Correlations between METTL7B expression and the TMB and MSI in various cancers. A Radar map of the correlation between METTL7B expression and the TMB. B Radar map of the correlation between METTL7B expression and MSI

Fig. 8

GSEA for comparing KEGG pathways and HALLMARK terms between the low and high METTL7B groups. A Twenty-nine KEGG pathways were significantly enriched in the high METTL7B group. B The top 10 enriched HALLMARK terms in the high METTL7B group

Fig. 9

Knockdown of METTL7B inhibits migration, invasion, and EMT. A Relative expression of METTL7B in LGG and normal brain tissues. B The transfection efficiency of the METTL7B siRNA in HS683 and SHG44 cells, as measured using qRT-PCR. C–D Wound healing assays and Transwell assays indicated the migratory and invasive abilities of glioma cells after transfection. E Western blots showing levels of the Vimentin and N-cadherin proteins in HS683 and SHG44 cells after METTL7B knockdown with an siRNA. Data are represented as the mean values ± SD. * p < 0.05, and ** p < 0.01

Fig. 10

METTL7B alters the proliferation of LGG cells. A Colony formation experiments using HS683 and SHG44 showed reduced cell viability in the si-METTL7B group. B CCK-8 assays showed the suppressed proliferation ability of transfected LGG cells