In summary, the low expression and high methylation of SHOX2, RASSF1A, and PTGER4 were prevalent in LC patients, in which the methylation positivity rates of SHOX2 and RASSF1A genes were related to their pathological types and TNM staging conditions, while the methylation positivity rate of the PTGER4 gene was only related to the pathological types. Here, PTGER4 is linked to laryngotracheoesophageal cleft.