Although previous studies have identified DMRs in ESCC, tumor‐specific hyper‐DMRs were not found to be enriched in cancer‐related pathways.[22] Furthermore, a previous study primarily focused on the inverse relationship between DNA methylation and gene expression in ESCC.[23] Our study is the first to identify a positive correlation between the hypermethylation of UMRs and potentially oncogenic homeobox genes, thus highlighting the importance of DNA hypermethylation in regulating oncogenic genes in ESCC. Here, LBX1 is linked to neoplasm.