YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

Abstract

Immunotherapy is an effective treatment for many cancer types. However, YTHDF2 effects on the prognosis of different tumors and correlation with tumor immune infiltration are unclear. Here, we analyzed The Cancer Genome Atlas and Gene Expression Omnibus data obtained through various web-based platforms. The analyses showed that YTHDF2 expression and associated prognoses may depend on cancer type. High YTHDF2 expression was associated with poor overall survival in lower-grade glioma (LGG). In addition, YTHDF2 expression positively correlated with expression of several immune cell markers, including PD-1, TIM-3, and CTLA-4, as well as tumor-associated macrophage gene markers, and isocitrate dehydrogenase 1 in LGG. These findings suggest that YTHDF2 is a potential prognostic biomarker that correlates with LGG tumor-infiltrating immune cells.

Keywords: YTHDF2; biomarker; lower-grade glioma; prognosis; tumor-infiltrating.

Figure 1

YTHDF2 expression in different types of human cancers were determined with (A) the TIMER, (B) GEPIA, and (C) ONCOMINE databases. ***P<0.001, **P<0.01, *P<0.05.

Figure 2

Kaplan-Meier survival curves comparing YTHDF2 high and low expression (A, B) in LGG, (C, D) LIHC, and (E, F) SARC in datasets from the GEPIA database. (A) OS and (B) DFS survival curves in LGG (n = 256). (C) OS and (D) DFS survival curves in LIHC (n = 182). (E) OS and (F) DFS survival curves in SARC (n = 131). DFS, disease-free survival; LGG, lower-grade glioma; LIHC, liver hepatocellular carcinoma; SARC, sarcoma; OS, overall survival.

Figure 3

Correlation of YTHDF2 expression with immune infiltration level in (A) LGG, (B) LIHC, and (C) SARC. LGG, lower-grade glioma; LIHC, liver hepatocellular carcinoma; SARC, sarcoma.

Figure 4

Correlation of YTHDF2 expression with IDH1 level in LGG. (A) High IDH1 expression was correlated with poor OS in the LGG GEPIA dataset. (B) LGG patients with IDH1 mutations had superior OS in the dataset from cBioPortal for Cancer Genomics. (C) IDH1 mutation led to a superior OS in gliomas. (D) IDH1 expression was not correlated with OS in the AML in GEPIA dataset. (E, F) YTHDF2 expression had a positive relationship with IDH1 in LGG and AML. (G) The immune infiltration levels were higher in IDH1-wild-type than in IDH1-mutant LGG. AML, acute myeloid leukemia; LGG, lower-grade glioma; OS, overall survival.

Figure 5

Enrichment analysis of YTHDF2 functional networks in LGG by LinkedOmics. (A) Volcano plot of genes differentially expressed in correlation with YTHDF2. (B, C) Heat maps of genes positively and negatively correlated with YTHDF2 (top 50). (D) KEGG pathway analysis of YTHDF2 by GSEA. (E) Panther pathway analysis of YTHDF2 by GSEA. (F) Reacmoe pathway analysis of YTHDF2 by GSEA. (G) Wiki pathway analysis of YTHDF2 by GSEA.