Expression Of CLDN3 In Esophageal Squamous Cell Carcinoma And Its Relationship With Clinical Pathology And Tumor Recurrence

Background and ObjectivesChina is one of the countries with the highest esophageal cancer in the world, among which the proportion of esophageal squamous cell carcinoma (ESCC) is more than 90%. There are many therapies to treat esophageal squamous cell carcinoma, and the surgical treatment is the main treatment at present. Despite the current treatments have made great progress, but due to the limitations of the current inspection apparatus and means and a majority of patients for medical treatment attitude is not positive enough, patients are often in the mid-late stage when they feel uncomfortable, which lead to the poor treatment effect and the low five-year survival rate. TNM staging is commonly used to assess the prognosis of patients, but the accuracy and sensitivity are still low. Therefore, it is important to find the relevant tumor markers to guide the prevention and clinical treatment of esophageal cancer. In recent years, there are some studies show that claudins(CLDN) are abnormally expressed in a variety of epithelial tumor cells,such as breast cancer, ovarian cancer, gastric cancer,prostate cancer and so on, but the occurrence and development of claudins’expression in esophageal carcinoma and the related research is less, so we investigate the expression of Claudin-3 in esophageal squamous cell carcinoma and biological function of cellular levels to explore its relationship with the clinical pathology and recurrence of tumors.Materials and methodsThe data of 113 cases of esophageal squamous cell carcinoma of the middle thoracic esophagus were collected and analyzed. The expression of Claudin-3 in esophageal squamous cell carcinoma was detected by immunohistochemical staining. The relevance judgment was tested by chi square, the survival rate was calcalmed by Kaplan-meier method and the difference was determined by the log-rank analyze.The Cox regression analysis was performed to determine the independent risk factors for lymph-metastastic recurrence. The KYSE450 esophageal squamous cell carcinoma cell line of Claudin-3 gene was silenced by virus transfection of siRNA,RT-PCR and Western blot were tested for transfection of Claudin-3 mRNA and protein expression, and CCK-8 assay and Transwell were used to observe cells transfection in biological function changes.ResultsIn 113 cases of esophageal squamous cell carcinoma,36 cases were positive for Claudin-3 expression, the positive rates in T1, T2 and T3+T4a groups were 56.5% (13/23),29.1%(16/55) and 20%(7/35) (P=0.012), respectively. The positive rates of Claudin-3 expression in lymph node metastasis negative group and positive group were 43.1%(22/51) and 22.6%(14/62) (P=0.020), respectively. The positive expression rates of Claudin-3 in the recurrent negative group and positive group were 42.1%(24/57) and 21.4%(12/56) (P=0.018), respectively. In the high-middle differentiation group and low differentiation group, the positive expression rates of Claudin-3 were 43.1%(22/51) and 22.6%(14/62) (P=0.020), respectively. The 5 year survival rate of Claudin-3 expression negative group was 35.1%, and the positive group was 69.4%(P=0.001), respectively. Lymph node metastasis (P=0.002), T stage (P=0.010) and negative expression of Claudin-3 (P=0.049) are independent prognostic factors. RT-PCR and blot Western confirmed that Claudin-3 gene silencing, the proliferation、migration and invasion abilities of esophageal squamous cell carcinoma cell were significantly enhanced.ConclusionsThe low expression of Claudin-3 metastasis in esophageal squamous cell carcinoma correlates with tumor differentiation, T stage and lymph node. The 5 year survival rate of Claudin-3 expression negative patients was significantly lower than that of the positive patients. Lymph node metastasis, T stage and negative expression of Claudin-3 were independent prognostic factors. The expression of Claudin-3 can inhibit the growth and migration of tumor cells. Claudin-3 can be used as a molecular marker to predict tumor recurrence in patients with cancers.