When considering alterations at pathway level, genes involved in cell cycle regulation (such as TP53, CCND1, CDK6, RB1, and CDKN2A) were frequently altered in the early stage of ESCC, whereas genes in RTK/RAS/PI3K tended to undergo alterations throughout the process of ESCC evolution [44]. Here, TP53 is linked to esophageal squamous cell carcinoma.