The RNA Methylation Modification 5-Methylcytosine Impacts Immunity Characteristics, Prognosis and Progression of Oral Squamous Cell Carcinoma by Bioinformatics Analysis

Abstract

Disorders pertaining to 5-methylcytosine (m5C) modifications are involved in the pathological process of many diseases. However, the effect of m5C on the tumorigenesis and progression of oral squamous cell carcinoma (OSCC) remains unclear. In this study, we integrated the genomic and clinical data of 558 OSCC samples to comprehensively evaluate m5C modification patterns. Based on 16 m5C methylation regulators, two m5C modification clusters were identified with distinct tumor immune microenvironment (TIME) characteristics and prognosis in OSCC. We then performed weighted gene co-expression network analysis (WGCNA) to identify m5C modification cluster-related modules. Genes in the selected module were chosen to construct the m5Cscore scoring system for evaluating m5C modification pattern in individual OSCC patients. Patients with a high m5Cscore had higher immune, stromal, and ESTIMATE scores; lower tumor purity score; lower immune activity; and higher tumor mutational burden. The overall survival rate and progression-free survival rate were markedly worse and the tumor recurrence rate was higher in OSCC patients with a high m5Cscore. Furthermore, patients with oral leukoplakia who also had a high m5Cscore had a higher risk of deterioration to OSCC. This study demonstrated that m5C modification patterns might affect the TIME in OSCC. m5Cscore may provide a new approach for predicting the prognosis and progression of OSCC.

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma

“…Furthermore, m5C methylation can also participate in the regulation of the TME. Gao et al [ 44 ] revealed that patients with oral squamous cell carcinoma with high m5C methylation scores had lower immune activity and a poor prognosis. What roles do m5C-related lncRNAs play in the TME?…”

Comprehensive Analysis of 5-Methylcytosine (m5C) Regulators and the Immune Microenvironment in Pancreatic Adenocarcinoma to Aid Immunotherapy

“…The results of the present study showed that there was no significant correlation between the m 5 C score and TMB, indicating that the m 5 C score is independent of TMB. It has been reported in previous studies low m 5 C score was related to a better prognosis of oral squamous cell carcinoma and papillary thyroid carcinoma patients ( 19 , 70 ). In our study, high m 5 C score indicated better immunotherapy response and prognosis.…”

“…For example, in CD4 + T cells from patients with SLE, the levels of the m 5 C writer NSUN2 and methylated m 5 C genes were found to be decreased ( 13 ). In cutaneous melanoma, lung adenocarcinoma, lung squamous cell carcinoma, and other cancer types, bioinformatic analysis have shown that m 5 C regulators modulate the tumor immune microenvironment, act as immunotherapy indicators and were related to patients’ prognosis ( 14 – 19 , 22 , 60 – 64 ). These studies firmly proved that m 5 C regulators were differentially expressed and modulated the immunotherapy response in multiple cancers.…”

“…Moreover, these lncRNAs were found to modulate the TME and predict the survival status of patients ( 14 ). Additionally, some bioinformatics analyses also indicated m 5 C modification regulates the TME and affects tumor progression ( 15 – 19 ). In PAAD, the decreased level of the m 5 C regulator NSUN6 represses tumor proliferation ( 20 ).…”

Identification of the Expression Patterns and Potential Prognostic Role of 5-Methylcytosine Regulators in Hepatocellular Carcinoma

“…In addition, Gao et al ( Gao et al, 2019 ) found that high expression of NSUN2 could promote the proliferation and tumorigenesis of gallbladder carcinoma cells both in vitro and in vivo by closely cooperating with ribosomal protein L6. Recently, the role of m5C modification in cancers, including lung cancer, colon carcinoma, bladder cancer, and thyroid carcinoma, has been explored ( Pan et al, 2021a ; Pan et al, 2021b ; Chen et al, 2021 ; Gao et al, 2021 ; Geng et al, 2021 ; Gu et al, 2021 ; Hu et al, 2021 ; Li et al, 2021 ; Liu et al, 2021 ; Xu et al, 2021 ). In addition, He et al ( He et al, 2020a ) built a gene signature including 2 m5C regulators and found that it could effectively predict the prognosis of HCC.…”