Targeted bisulfite sequencing identified a panel of DNA methylation-based biomarkers for esophageal squamous cell carcinoma (ESCC)

Clinical Epigenetics
Weilin PuMinghua Wang


DNA methylation has been implicated as a promising biomarker for precise cancer diagnosis. However, limited DNA methylation-based biomarkers have been described in esophageal squamous cell carcinoma (ESCC). A high-throughput DNA methylation dataset (100 samples) of ESCC from The Cancer Genome Atlas (TCGA) project was analyzed and validated along with another independent dataset (12 samples) from the Gene Expression Omnibus (GEO) database. The methylation status of peripheral blood mononuclear cells and peripheral blood leukocytes from healthy controls was also utilized for biomarker selection. The candidate CpG sites as well as their adjacent regions were further validated in 94 pairs of ESCC tumor and adjacent normal tissues from the Chinese Han population using the targeted bisulfite sequencing method. Logistic regression and several machine learning methods were applied for evaluation of the diagnostic ability of our panel. In the discovery stage, five hyper-methylated CpG sites were selected as candidate biomarkers for further analysis as shown below: cg15830431, P = 2.20 × 10-4; cg19396867, P = 3.60 × 10-4; cg20655070, P = 3.60 × 10-4; cg26671652, P = 5.77 × 10-4; and cg27062795, P = 3.60 × 10-4. In the validation stage, t...Continue Reading


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