In esophageal cancer, ctDNAs targeting CASZ1, CDH13, and ING2 genes show significant high level of hypermethylation in ESCC patients but mild level in healthy controls, whereas dysregulation of 5-hydroxymethylcytosine expression on ctDNAs also has remarkable sensitivity in screening ESCC; therefore, ctDNA detection based on these two different patterns is highly likely to identify the early-stage esophageal cancer (234, 235). This evidence concerns the gene CASZ1 and esophageal squamous cell carcinoma.