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Updated: Apr 26, 2026
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
The decreased expression of protease-activated receptor 4 in esophageal squamous carcinoma
Abstract:
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.
Insights
Protease-activated receptor 4 (PAR4) is decreased in esophageal squamous cancer, potentially due to promoter hypermethylation. This PAR4 expression loss may serve as a diagnostic marker for tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Protease-activated receptors (PARs) are G-protein coupled receptors implicated in cancer development.
- The specific role of PAR4 in esophageal squamous cancer progression remained unclear.
Purpose of the Study:
- To investigate the expression levels of PAR4 in esophageal squamous cancer.
- To explore the correlation between PAR4 expression and clinicopathological features.
- To examine the methylation status of the PAR4 promoter in esophageal cancer.
Main Methods:
- Real-time PCR (n=28), Western blot, and tissue microarrays (n=78) were used to assess PAR4 expression.
- DNA methylation analysis of the PAR4 promoter in esophageal cancer cell lines and normal epithelial cells was performed.
Main Results:
- PAR4 expression was significantly downregulated in esophageal squamous cancer tissues compared to noncancerous tissues.
- Reduced PAR4 expression was particularly evident in poorly differentiated and metastatic tumors.
- Hypermethylation of the PAR4 promoter was observed in esophageal cancer cells, contrasting with hypomethylation in normal cells.
Conclusions:
- Downregulation of PAR4 is frequent in esophageal squamous cancer and may be linked to promoter hypermethylation.
- PAR4 expression levels could serve as a potential molecular marker for esophageal tumor diagnosis and progression.
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