Journal
AGING-US
Volume 11, Issue 23, Pages 11640-11658Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.102569
Keywords
DNA methylation; biomarker; Barrett's esophagus; esophageal cancer; LASSO
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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.
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