Abstract

Background DNA methylation is an important part of epigenetic modification, and its abnormality is closely related to esophageal adenocarcinoma (EAC). This study was aimed at using bioinformatics analysis to identify methylation-driven genes (MDGs) in EAC patients and establish a risk model as a biological indicator of EAC prognosis. Method Downloaded EAC DNA methylation, transcriptome, and related clinical data from TCGA database. MethylMix was used to identify MDGs. R package clusterProfiler and the ConsensusPathDB online database were used to analyze the rich functions and pathways of these MDGs. The prognostic risk model was established by univariate Cox regression, Lasso regression, and multivariate Cox regression analysis. Finally each MDG in the model were carried out through the survival R package. Results A total of 273 MDGs were identified, which were enriched in transcriptional regulation and embryonic organ morphogenesis. Cox regression analysis established a risk model consisting of GPBAR1, OLFM4, FOXI2, and CASP10. In addition, further survival analysis revealed that OLFM4 and its two related sites were significantly related to the EAC patients' survival. Conclusion In summary, this study used bioinformatics methods to identify EAC MDGs and established a reliable risk prognosis model. It provided potential biomarkers for the early treatment and prognosis evaluation of EAC.

Highlights

  • Esophageal cancer (EC) is a common malignant tumor of the digestive system

  • We assessed the correlation between the methylation level and the expression level of each gene based on the MethylMix software package

  • Drinking and smoking are the two main risk factors for esophageal squamous cell carcinoma (ESCC) [26], and the pathogenesis of esophageal adenocarcinoma (EAC) is mainly related to the abnormal proliferation of esophageal epithelial cells caused by gastroesophageal reflux disease (GERD) [27]

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Summary

Introduction

Esophageal cancer (EC) is a common malignant tumor of the digestive system. Its global morbidity and total mortality ranked seventh and sixth, respectively, in 2018 [1]. There are two main histological subtypes of EC, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). DNA methylation is an important part of epigenetic modification, and its abnormality is closely related to esophageal adenocarcinoma (EAC). This study was aimed at using bioinformatics analysis to identify methylation-driven genes (MDGs) in EAC patients and establish a risk model as a biological indicator of EAC prognosis. This study used bioinformatics methods to identify EAC MDGs and established a reliable risk prognosis model. It provided potential biomarkers for the early treatment and prognosis evaluation of EAC

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