The m6A reader protein YTHDC2 is a potential biomarker and associated with immune infiltration in head and neck squamous cell carcinoma

Abstract

Background Increasing evidence has shown that N6-methyladenosine (m6A) RNA methylation regulators have important biological functions in human cancers. However, there are few studies on the value of m6A reader protein YTHDC2 in the diagnosis and tumor-infiltrating of head and neck squamous cell carcinoma (HNSCC). Therefore, it is important to understand the potential clinical value of YTHDC2 in the prognosis and immune infiltration of HNSCC. Methods In this study, gene expression profiles and the corresponding clinical information of 270 HNSCC patients were downloaded from the Gene Expression Omnibus (GEO) database. The gene co-expression network was established to verify whether YTHDC2 was related to the prognosis of HNSCC and verified again in the public database. The correlations between YTHDC2 and immune infiltration was investigated via Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). Results The results showed that YTHDC2 appeared in the blue module related to survival time and survival state and had a close correlation with the prognosis and immune infiltration level of HNSCC in public database. Patients with low expression of YTHDC2 had poor overall survival (OS) and recurrence-free survival (RFS) than those with high expression. In addition, the expression of YTHDC2 was positively correlated with the level of CD4+ T cell subpopulations infiltration in HNSCC. Conclusions Through this study, we found that YTHDC2 is a tumor suppressor gene with high expression in normal tissues and low expression in tumor tissues. In addition, YTHDC2 is correlated with the immune infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells in HNSCC, which may become a potential marker for prognosis and immune infiltration of HNSCC.

Roles of RNA Methylation on Tumor Immunity and Clinical Implications

“…Through the analysis of gene expression and prognosis of HNSCC patients in GEO, Oncolnc, Kaplan-Meier plotter, TIMER and other databases, it was found that YTHDC2 could be an independent tumor suppressor gene to judge the prognosis of HNSCC, and the expression level of YTHDC2 was positively correlated with the infiltration level of CD4+T cell subsets. However, the correlation between YTHDC2 and CD4+T cell subsets and its specific mechanism need further experimental study ( 120 ).…”

Targeting SLC3A2 subunit of system XC− is essential for m6A reader YTHDC2 to be an endogenous ferroptosis inducer in lung adenocarcinoma

“…Unlike writers and erasers, readers belong to the category of RNA binding proteins, recognizing and guiding m 6 A modi ed RNAs for subsequent processing [20,21], thereby they are the executors of m 6 A. YTHDC2 is such an m 6 A reader identi ed in 2017 [22] and its YTH domain is essential for recognizing and binding with the m 6 A-modi ed target RNAs [23,24]. Dysregulation of YTHDC2 has been linked with tumorigenesis and progression [25,26]. Our previous study also demonstrated that YTHDC2 exhibits a tumor suppressor activity to suppress antioxidant function of LUAD cells via accelerating SLC7A11 mRNA decay [24].…”

The Biological Function, Mechanism, and Clinical Significance of m6A RNA Modifications in Head and Neck Carcinoma: A Systematic Review

“…YTHDC2 expression is significantly correlated with B cells, CD4 + T cells, neutrophils, and dendritic cells, but not with macrophage infiltration in HNSCC ( Li et al, 2020 ), indicating that YTHDC2 may play an important role in immune cells in the tumor microenvironment, especially CD4 + T cells and dendritic cells. Further analysis revealed that changes in the somatic copy number of recognized m6A regulator-based signals significantly affect the infiltration of B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells in HNSCC ( Yi et al, 2020b ), consistent with the hypothesis that this m6A regulatory protein plays a key role in HNSCC development.…”

“…However, the survival curves obtained using EPIC and CIBERSORT algorithms indicated that patients with low YTHDC2 expression and low CD4 + T or CD4 + natural T cell infiltration had a better prognosis than those with high YTHDC2 expression and high CD4 + T or CD4 + natural T cell infiltration. Moreover, when the effect of YTHDC2 expression on HNSCC prognosis was evaluated, tumors with high YTHDC2 expression displayed a better prognosis than those with low YTHDC2 expression ( Li et al, 2020 ). Together, these findings suggest that different CD4 + T cell subsets may exert different effects on the prognosis of HNSCC.…”