Changes in Claudin-4 expression and tight junction integrity in human esophageal cancer: A Systematic Review

Background: Esophageal cancer is one of the most common cancers worldwide. Because this disease is usually diagnosed in advanced stages, its treatment is challenging and the survival rate of patients is relatively low. One of the parts that is disturbed in the tumor tissue of esophageal cancer is the tight connections between cells. Claudin-4 (CLDN-4) is one of the tight junction regulatory proteins whose changes are involved in cancer formation. In this systematic review, we examine the changes in CLDN-4 and the factors that affect its level in samples and cell lines related to esophageal cancer. Methods: Scopus, PubMed, and Web of Science databases were searched for articles that examined CLDN-4 gene and protein expression in patients with esophageal cancer or cell lines related to esophageal cancer. A number of 202 manuscripts were obtained in the beginning, and after screening and applying the inclusion and exclusion criteria, six studies remained. Results: Six studies, including 596 patients and seven cell lines related to esophageal tissues, were included in this systematic review. The studies were related to Japan, South Korea, China, and Finland. In these studies, the level of CLDN-4 in cancer samples related to esophageal cancer and their location in esophageal tissue cells have been examined. Conclusion: In summary, it can be concluded that the change in the level of CLDN-4 in the tumor tissues of esophageal cancer altered the tight junctions from the normal state in the normal esophageal tissues, leading to a change in normal barrier function. However, considering the conflicting results in the reports, more studies are needed to accurately interpret the role of CLDN-4 in esophageal cancer.