We selected the second-ranked HOXL subclass homeobox family for further analysis, as more than half (n = 24, 66.67%) of the genes were identified as ESCC-DMGs, which is the highest than the other two families (32/57 = 56.14% for NKL subclass and 70/648 = 10.8% for Zinc fingers C2H2-type). Here, GLIS2 is linked to esophageal squamous cell carcinoma.