The Expression Of CLDN4 In Laryngeal Squamous Cell Carcinoma

Laryngeal carcinoma is one of the most common head and neck cancers. Laryngeal squamous cell carcinoma is the dominant type of laryngeal malignancy, accounted for more than 98% of laryngeal carcinoma. In recent years, studies have shown that CLDN4 expresses abnormally in many kinds of epithelial tumors. For example, CLDN4 is up regulated in pancreatic carcinoma, breast carcinoma and stomach carcinoma, while down regulated in carcinoma of urinary bladder and renal cell carcinoma. In consequence, we infer that its expression plays a role in tumorigenesis and metastasis, but there are no reports about its expression in laryngeal carcinoma. As reported, DNA methylation can regulate the expression CLDNs, methylated DNA can interact with Mecp-2, leading to suppression of gene transcription. The methylation of CLDN4 promoter region can lead to gene silencing CLDN4 in ovarian cancer and bladder cancer, but CLDN4 expression in laryngeal is subject to the regulation of DNA methylation is still unclear.Aim: To assess the expression of CLDN4 in laryngeal carcinoma,and further explore the mechanism of regulating the expression of CLDN4.Methods: The expression of CLDN4 in 95 cases of laryngeal squamous cell carcinoma and 95 cases of tissue adjacent to the tumor wasdetected by immunohistochemistry(S-P) method, and the expression of Mecp-2 in 95 cases of laryngeal squamous cell carcinoma and 95 cases of tissue adjacent to the tumor was detected by immunohistochemistry. The association between CLDN-4 and Mecp-2 was analyzed by statistically.Treated laryngeal carcinoma cell line hep-2 with 5-aza-dc, then detected the expression of CLDN-4 with RT-PCR and western blot analysis.Furthermore, wound healing test and transwell were carried out to detect the migration and invasion of laryngeal carcinoma cell line hep-2.Results: The expression of CLDN4 in laryngeal cancer was lower than the tissue adjacent to the tumor, Meanwhile, the expression of CLDN4 was possitively related to the differentiation of the tumor.Up-regulated Mecp-2 was detected in laryngeal cancer, and the expression of Mecp-2 wasn’t significantly related to differentiation of the tumor. After demethylated with 5-aza-dc, the expression of CLDN-4 was up regulated in hep-2, and the migration and invasion of hep-2 were significantly decreased.Conclusion:1. The expression of CLDN4 in laryngeal carcinoma were down regulated, and correlated with the expression of Mecp-2;2. 5-aza-dC can increase the expression of CLDN4 in hep-2 cells and inhibit migration and invasion capacity of the cells;3. The expression of CLDN6 was down-regulated may related withDNA methylation, and the down-regulated of CLDN6 would lead to the occurrence and development of laryngeal cancer.