Development and Validation of an m6A RNA Methylation Regulator-Based Signature for Prognostic Prediction in Cervical Squamous Cell Carcinoma.

Jingxin Pan,Lichao Xu,Hongda Pan

doi:10.3389/fonc.2020.01444

Abstract

Background: Cervical squamous cell carcinoma (CESC) is one of the most common causes of cancer-related death worldwide. N6-methyladenosine (m6A) plays an important role in various cellular responses by regulating mRNA biology. This study aimed to develop and validate an m6A RNA methylation regulator-based signature for prognostic prediction in CESC.Methods: Clinical and survival data as well as RNA sequencing data of 13 m6A RNA methylation regulators were obtained from The Cancer Genome Atlas (TCGA) CESC database. Consensus clustering was performed to identify different CESC clusters based on the differential expression of the regulators. LASSO Cox regression analysis was used to generate a prognostic signature based on m6A RNA methylation regulator expression. The effect of the signature was further explored by univariate and multivariate Cox analyses.Results: Four regulators (RBM15, METTL3, FTO, and YTHDF2) were identified to be aberrantly expressed in CESC tissues. A prognostic signature that includes ZC3H13, YTHDC1, and YTHDF1 was developed, which can act as an independent prognostic indicator. Significant differences of survival rate and clinicopathological features were found between the high- and low-risk groups. The results of bioinformatics analysis were then validated in the clinical CESC cohort by qRT-PCR and immunohistochemistry staining.Conclusion: In the present study, we developed and validated an m6A RNA methylation regulator-based prognostic signature, which might provide useful insights regarding the development and prognosis of CESC.

Highlights

Cervical squamous cell carcinoma (CESC) is the fourth most commonly diagnosed cancer and the fourth leading cause of cancer-associated mortality in women worldwide [1]
The mRNA expression levels of three regulators (RBM15, METTL3, and YTHDF2) were significantly increased, and FTO was decreased in CESC compared with normal tissues
Correlations among the mRNA expression levels of 13 m6A RNA methylation regulators were analyzed by Pearson correlation analysis (Figure 2B), and the protein–protein interactions (PPIs) were retrieved via String database (Figure 2C)

Summary

Introduction

Cervical squamous cell carcinoma (CESC) is the fourth most commonly diagnosed cancer and the fourth leading cause of cancer-associated mortality in women worldwide [1]. M6A RNA modification plays crucial roles in many processes of gene regulation such as mRNA stability, splicing, and translation [3]. Emerging evidence has revealed the cancer promoter or suppressor role of m6A regulators in the development of various malignancies [5,6,7], whereas the correlation between prognosis of CESC and m6A RNA methylation regulators is still unclear. Cervical squamous cell carcinoma (CESC) is one of the most common causes of cancer-related death worldwide. N6-methyladenosine (m6A) plays an important role in various cellular responses by regulating mRNA biology. This study aimed to develop and validate an m6A RNA methylation regulator-based signature for prognostic prediction in CESC

Objectives

Methods

Results

Conclusion