Research Paper Volume 11, Issue 23 pp 11640—11658

Specific DNA methylation markers in the diagnosis and prognosis of esophageal cancer

DaPeng Li 1, , Lei Zhang 1, , YuPeng Liu 1, , HongRu Sun 1, , Justina Ucheojor Onwuka 1, , ZhiGang Zhao 2, , WenJing Tian 1, , Jing Xu 1, , YaShuang Zhao 1, *, , HongYu Xu 3, *, ,

  • 1 Department of Epidemiology, Public Health School of Harbin Medical University, Harbin 150081, China
  • 2 Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
  • 3 Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
* Equal contribution

received: October 9, 2019 ; accepted: November 23, 2019 ; published: December 13, 2019 ;

https://doi.org/10.18632/aging.102569
How to Cite

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The early diagnosis and accurate prognosis prediction of esophageal cancer is an essential part of improving survival. However, these diseases lack effective and specific markers. A total of 1,744 samples of HumanMethylation450 data were integrated to identify and validate specific methylation markers for esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) as well as for Barrett’s esophagus (BE) using The Cancer Genome Atlas and the Gene Expression Omnibus. The diagnostic and prognostic methylation classifiers were constructed by moderated t-statistics and the least absolute shrinkage and selection operator method. The diagnostic methylation classifier using 12 CpG sites was constructed in training set (377 samples) that could effectively discriminate samples of BE, EAC, and ESCC from normal tissue (AUC = 0.992), which achieved highly predictive ability in both internal (187 samples, AUC = 0.990) and external validation (184 samples, AUC = 0.978). The prognostic methylation classifier with 3 CpG and 2 CpG sites for EAC and ESCC respectively, could accurately estimate the prognosis of an individual patient and improved the predictive ability of the tumor node metastasis staging system. Overall, our study systematically analyzed large-scale methylation data and provided promising markers for the diagnosis and prognosis of esophageal cancer.

Abbreviations

ESCC: Esophageal squamous cell carcinoma; EAC: Esophageal adenocarcinoma; BE: Barrett’s esophagus; HNSC: Head and neck squamous cell carcinoma; STAD: Stomach adenocarcinoma; NSE: Normal squamous esophagus; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; FDR: False discovery rate; LASSO: Least Absolute Shrinkage and Selection Operator; CI: Confidence interval; ROC: Receiver Operating Characteristic; AUC: Area Under; DMC: Differential methylation CpG site.