The decreased expression of protease-activated receptor 4 in esophageal squamous carcinoma.

Protease-activated receptors (PARs) are a unique family of G-protein coupled receptors. PAR4, a member of PARs family, was reported to be related to the development of cancers. Whether PAR4 plays a role in the progress of esophageal squamous cancer is unknown. In this study, differential expression of PAR4 in esophageal squamous cancer was measured by real-time PCR (n = 28), western blot and tissue microarrays (n = 78). The results showed that PAR4 expression was remarkably decreased in esophageal squamous cancer tissues compared with the matched noncancerous tissues, especially in low differentiation and positive distant metastasis carcinoma tissues. Furthermore, the methylation level of PAR4 promoter in esophageal cancer cells and normal epithelial cells was determined. Human esophageal cancer cells TE-1 displayed significant hypermethylation of 19 CpG sites, but pronounced hypomethylation of the sites in esophageal epithelial cells HEEpiC. The results suggested that down-regulation expression of PAR4 occurs frequently in esophageal squamous cancers, and the loss of PAR4 expression may partly result from hypermethylation of the PAR4 promoter. That PAR4 expression difference in tumor progression possibly makes PAR4 become a molecular mark of tumor diagnosis.