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

Li Gao,Ru Chen,Masanobu Mizuta,Lei Zhou,Xinsheng Huang,Yo Kishimoto,Masahiro Sugimoto,Koichi Omori

doi:10.3389/fbioe.2021.760724

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.

Highlights

Mediator proteins known as “writers,” “erasers,” and “readers” (Trixl and Lusser, 2019)
We analyzed the roles of m5C regulators in the tumor immune microenvironment (TIME) and prognosis in Oral squamous cell carcinoma (OSCC) and developed the m5Cscore scoring system
In the TIME of OSCC, immune cells such as tumor-infiltrating lymphocytes (TILs), dendritic cells (DCs), natural killer (NK) cells, and T-cells are in an inactive state (Jewett et al, 2006)

Summary

Introduction

Mediator proteins known as “writers,” “erasers,” and “readers” (Trixl and Lusser, 2019). Chen et al found that NSUN2 and YBX1 promoted oncogenesis in human bladder urothelial carcinoma by targeting the m5C methylation site in the untranslated region of HDGF3 (Chen et al, 2019a). Further investigation into the mechanisms involved in the oncogenesis and development of OSCC might help improve diagnostic accuracy at an early stage, as well as the treatment effective rate. It has been verified that dysfunction of the tumor immune microenvironment (TIME) affects the oncogenesis and development of OSCC (Quan et al, 2020) (Bhat et al, 2021). Genes in the selected module were chosen to construct the m5Cscore scoring system for evaluating m5C modification pattern in individual OSCC patients. The m5C modification patterns and the m5Cscore scoring system might help in the prediction of the prognosis and progression of OSCC

Methods

Results

Conclusion