Numerous studies have reported elevated Hes1 expression in CRC: mRNA levels in CRC tissues are generally higher than those in adjacent normal tissues (38, 73, 125, 147); immunohistochemistry has demonstrated a gradient increase in average Hes1 immunoreactivity from normal mucosa to adenoma to cancerous regions (79); epigenetic analysis indicates that low methylation of the Hes1 promoter correlates with its overexpression and is significantly associated with histological grade progression, lymph node metastasis, and poor prognosis (125). Here, HES1 is linked to adenoma.