High Expression of Claudin-4 Is Associated with Synchronous Tumors in Patients with Early Gastric Cancer

Claudin (CLDN) is a tight junction protein found in human epithelial cells and its altered expression is known to be associated with the progression of gastric cancer. We aimed to investigate the differential expression of CLDN-4 in early gastric cancer (EGC) according to its clinicopathological characteristics. We enrolled 53 patients with EGC who underwent surgical gastric resection from January 2007 to December 2018. The staining intensity of the tumor cells was scored as 0-3, and the percentage of staining was scored as 0-5; high expression was defined if the intensity plus percentage score was 7 or 8, and low expression was defined if the score was 0-6. Among the 53 patients, 16 (30.2%) showed low CLDN-4 expression, while 37 (69.8%) had high CLDN-4 expression. High CLDN-4 expression was significantly associated with intestinal-type EGC (low: 12.5% vs. high: 56.8%, p = 0.003), open-type atrophic change (low: 60.0% vs. high: 90.9%, p = 0.011), and the presence of synchronous tumors (0 vs. 32.4%, p = 0.010), and all 12 EGCs with synchronous tumors showed high CLDN-4 expression. However, expression of CLDN-3, a typical intestinal phenotype CLDN, was neither correlated with CLDN-4 expression nor associated with synchronous tumors. Taken together, high CLDN-4 expression may be considered as an auxiliary tool for screening synchronous tumors in patients with EGC.

Automated summary

This study investigated the differential expression of CLDN-4 in early gastric cancer (EGC) and found a significant association between high CLDN-4 expression and intestinal-type EGC, open-type atrophic change, and the presence of synchronous tumors. These findings suggest that CLDN-4 may serve as an auxiliary tool for screening synchronous tumors in patients with EGC.