Previous pan-cancer analyses have shown that DNA methylation plays a predominant role in dysregulating TFs in general and the homeobox family in particular.29,45 Since TFs are “master regulators” of biological processes and pathways critical for the development and differentiation of specific cell types46 and their defining functions,47 DNA methylation associated with TF dysregulation could happen at an early or even precancerous stage of ESCC, making them good candidates for early diagnosis markers. This evidence concerns the gene LBX1 and cancer.