In ESCC, the most frequently mutated genes were NFE2L2, NOTCH1, EP100, FAT1, NFKBIA, KAT6A, and KMT2D. In EAC, the genes that exhibited the highest mutation rates were SMAD4, KRAS, ARID1A, and DYNC2H1. The differences in mutated genes between the two groups were significant (q < 0.05) (Figure 4). This evidence concerns the gene SMAD4 and esophageal squamous cell carcinoma.