Abstract: Hairy/enhancer of split 1 (HES1) is a basic helix–loop–helix transcriptional repressor. Aberrant demethylation has been considered a common mechanism of tumor promoter gene activation. In the current study, we aimed to investigate the methylation status of the HES1  promoter and correlations with clinicopathological parameters and prognosis in colorectal cancer (CRC). The expression of HES1 in 50 paired CRC specimens and adjacent normal tissues was determined by using quantitative real-time polymerase chain reaction and immunohistochemical analysis. Moreover, DNA methylation status was evaluated through methylation-specific polymerase chain reaction and bisulfite sequencing. The correlation of methylation status with HES1 expression level and clinicopathological parameters was statistically analyzed in CRC patients. Our data showed that the methylation level of HES1  was significantly decreased and negatively correlated with HES1 expression in CRC tissues. Moreover, HES1  hypomethylation was associated with a poor histological grade, Dukes’ classification, lymph node metastasis, and clinical stages (P <0.05). Furthermore, survival analyses revealed that a decreased methylation status of HES1  was linked to poor prognosis of CRC patients. In conclusion, promoter hypomethylation upregulates HES1 expression and plays a critical role in the progression and prognosis of CRC patients.
Keywords: colorectal cancer, HES1 , hypomethylation, prognosis, progression