Comprehensive analysis of exome sequencing in tumor-normal paired ESCC tissues identified 22 significantly mutated driver genes (SMGs) (including TP53, NOTCH1, NFE2L2, KMT2D, CDKN2A, ZNF750, PIK3CA, RB1, FAT1, EP300, FBXW7, TGFBR2, AJUBA, CREBBP, FAT2, NOTCH3, PTCH1, KDM6A, FAM135B, TET2, PTEN, and ADAM29), along with other somatic genomic alterations contribute to the development of ESCC,3 but even so, there is still a lack of effective biomarkers for early detection, and the 5-year survival rate of ESCC patients is < 20%.4 This evidence concerns the gene KMT2D and esophageal squamous cell carcinoma.