In this study, the transforming growth factor-β (TGF-β) receptor type II gene (TGFBR2), a key mediator of TGF-β signaling which has been implicated in ESCC carcinogenesis, was identified as a putative tumor suppressor in ESCC based on WGBS of paired and unpaired ESCC tissues. This evidence concerns the gene TGFB1 and esophageal squamous cell carcinoma.