Despite the tumor-promoting function of WNT5a/FZD2 pathway was found in previous study, WNT5A is frequently silenced by promoter CpG methylation in ESCC (26, 35), indicating that WNT5A may not be a critical ligand binding to FZD2 in ESCC progression. The gene discussed is FZD2; the disease is esophageal squamous cell carcinoma.