The role of Hedgehog protein and gene methylation in the pathogenesis of esophageal cancer

Abstract

Objective To explore the role of the Hedgehog singaling in the pathogenesis of esophageal cancer. Methods Tissue samples of normal esophageal mucosa, low-grade dysplasia, high-grade dysplasia and esophageal cancer were collected.Immunohistochemical stain, Western-blot and RT-PCR were employed to detect the expression of Hedgehog protein and gene, methylation special PCR was used to detect the methylation status of Hedgehog gene. Results There was no difference in the expression of SHh protein among nornaml esophageal and low-grade dysplasia, high-grade dysplasia and esophageal cancer (LGD vs.N: t=1.96, P=0.67; HGD vs.EC: t=1.59, P=0.53). However, the expression of SHh protein in high-grade dysplasia and esophageal cancer was higher than that in normal esophageal mucosa and low-grade dysplasia(HGD vs.N: t=0.593, P=0.004; HGD vs.LGD: t=1.308, P=0.325; EC vs.N: t=0.292, P=0.000; EC vs.LGD: t=0.734, P=0.004). The expression of Hedgehog gene in esophageal cancer was higher than that in normal esophageal mucosa, low-grade dysplasia and high-grade dysplasia(EC vs.N: t=0.909, P=0.019, EC vs.LGD: t=0.398, P=0.007; EC vs.HGD: t=0.843, P=0.012). The gene methylation in esophageal cancer was lower than that in normal esophageal mucosa, low-grade dysplasia and high-grade dysplasia(EC vs.N: t=0.0340, P=0.000; EC vs.LGD: t=0.102, P=0.000; EC vs.HGD: t=0.367, P=0.018). Conclusion Hedgehog signaling may play a role in the pathogenesis and development of esophageal cancer, however, demethylation of Hedgehog gene may be one of the mechanism that cause the activity of oncogene in esophageal cancer. Key words: Esophageal Neoplasms; Hedgehog Proteins; DNA Methylation