The Expression Of Claudin-4 In Cholangiocarcinoma And Its Effect On The Biology Behavior Of Bile Duct Cancer Cell

Background:Cholangiocarcinoma derived from the biliary epithelial cell is the highly malignant tumor. According to its occurrence site, cholangiocarcinoma can be divided into intrahepatic, hilar and distal bile duct cancer and its incidence keeps elevating in recent years. It will be a great challenge to improve the therapeutic level and prognosis of cholangiocarcinoma. Currently, early surgical treatment is still the best treatment of bile duct cancer for prognosis. However, because of the lack of specifically diagnostic methods and detecting indexes, early diagnosis is difficult. In addition, the lesion of liver, the late shifting and the lack of effectively late treatments make prognosis is poor and median survival time is only 24 months after diagnosis. It is important for improving early diagnostic rate and therapeutic effect of cholangiocarcinoma to reach the pathogenesis of cholangiocarcinoma and look for specific markers of bile duct cancer.Claudin-4 is one member of integrin proteins’ family and is significant for maintaining the material transfer between normal cells and extra cells and keeping osmotic pressure of normal cells, and also plays an important role in regulating organs occurring and developing in embryonic and postnatal period. The abnormal expression of Claudin-4 is highly related to tumor development in many tumors. Most studies show that Claudin-4 is a cancer-promoting factor. Such as in lung cancer and ganstric cancer, Claudin-4 increases the invasion and metastasis of tumor and make poor prognosis. Some studies have shown that Claudin-4 had a tumor suppressor role. Such as in pancreatic cancer, Claudin-4 can inhibit the malignant activity of tumor cells and is associated with a better prognosis. The studies about Claudin-4 in cholangiocarcinoma are little and the relationship between Claudin-4 and cholangiocarcinoma is still unclear. So we analyzed the relationship between integrin protein (Claudin-4) and clinicopathological features of cholangiocarcinoma, and the impact of Claudin-4 in prognosis of patients and in biology behavior of cholangiocarcinoma cell.Methods:We used immunohistochemistry to detect the expressing strength and density of Claudin-4 in cancer tissues and adjacent tissues of 77 paired cholangiocarcinoma cases. Paired t test was used to compare expressed difference of Claudin-4 in tumor tissues and pericarcinomatous tissue, and chi-square test was used to analyze the correlation between expressed level of Claudin-4 and clinicopathological features of cholangiocarcinoma. Following up the survival time of patients with cholangiocarcinoma after surgery, we used Kaplan-Meier survival analysis to find the impact of Claudin-4 in survival.Results:The result of Immunohistochemistry showed that Claudin-4 expression was significantly increased in cancer tissues than adjacent tissues. We used siRNA technology to disturb the Claudin-4 expression in cholangiocarcinoma cells RBE and HCC9810, and observed its effect in biology behavior of cholangiocarcinoma cells. Claudin-4 expression was significantly correlated with tumor location and tumor differentiation, but showed no significant correlation with age, tumor size, TNM stage and vascular invasion. Kaplan-Meier analysis showed that survival rates were 29.8% in low expression of Claudin-4 and 21.1% in high expression of Claudin-4, but the difference was not statistically significant (X2=1.566, P= 0.211). After low expression of Claudin-4, proliferation, migration and invasion of the cells did not change significantly.Conclusion:In summary, the present study indicates that Claudin-4 is high expression in cholangiocarcinoma and can be used as a biological indicator of bile duct cell transforming to malignancy. But disturbing the expression of Claudin-4 had no significant impact on the biological behavior of cholangiocarcinoma cell RBE and HCC9810.