Identification of potential CpG sites for oral squamous cell carcinoma diagnosis via integrated analysis of DNA methylation and gene expression

Le Chen,Dong Wang

doi:10.1186/s12957-021-02129-1

Abstract

BackgroundOral squamous cell carcinoma (OSCC) accounts for more than 90% of the oral carcinomas and has a high fatality rate. This study aimed to identify potentially diagnostic biomarkers of OSCC through integrated analysis of DNA methylation and gene expression profiles.MethodsThe DNA methylation profiles of OSCC patients from The Cancer Genome Atlas (TCGA) were analyzed to screen patients with CpG island methylator phenotype (CIMP) and investigate the relationship between CIMP and survival probability of OSCC patients. Differential methylation and expression analyses of the paired OSCC tumor and paracancerous samples from TCGA were performed. Logistic regression model was established, and the accuracy of this diagnostic model for OSCC was evaluated in validation sets from Gene Expression Omnibus (GEO).ResultsOSCC patients with CIMP had lower survival probability than those without CIMP. The cg02860732 and cg04342955 were determined as candidate diagnostic methylation sites for OSCC. Logistic regression model was established based on cg02860732 and cg04342955 showed relatively high diagnostic accuracy in OSCC.ConclusionsA diagnostic model for OSCC was identified based on the methylation sites cg02860732 and cg04342955, which might be favorable for the diagnosis of OSCC.

Highlights

Oral squamous cell carcinoma (OSCC) is a malignant tumor occurring in the oral cavity accounts for more than 90% of the oral carcinomas [1]
Assessment of diagnostic methylation sites The logistic regression model for OSCC diagnosis was established based on the β values of the identified methylation sites in OSCC and paracancerous samples, using The Cancer Genome Atlas (TCGA) dataset as the training set
DNA methylation overview and its effect on OSCC prognosis A total of 1243 methylation sites were selected with the criteria of standard deviation (SD) > 0.2 in 70 OSCC patients and β < 0.05 in 5 paracancerous samples

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is a malignant tumor occurring in the oral cavity accounts for more than 90% of the oral carcinomas [1]. Except for the aberrant expressions of mRNA and lncRNA, epigenetics has been a promising field in cancer research, including DNA methylation which occurs in the CpG islands near gene transcription start sites [9]. Alteration of DNA methylation is able to affect the gene expression, as well as diverse molecular mechanisms; aberrantly methylated CpG sites are regarded as promising biomarkers in various cancers including OSCC [10, 11]. After comprehensively analyzing the two expression profiles, the downstream diagnosis could be found more accurately and reasonably based on the methylation molecular mechanism of OSCC. This study aimed to identify potentially diagnostic biomarkers of OSCC through integrated analysis of DNA methylation and gene expression profiles

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Conclusion