Prognostic significance of Claudin18.2 expression in gastric cancer: A large single-center cohort and meta-analysis.

Abstract

449 Background: Claudin 18.2 (CLDN18.2) is a novel treatment target for patients with unresectable or stage IV gastric cancer (GC). However, it remains controversial whether the expression of CLDN18.2 affects survival outcomes. We aimed to evaluate the clinicopathological significance and survival impact of CLDN18.2 expression in our institutional cohort and to validate these findings through a systematic review and meta-analysis. Methods: We retrospectively analyzed 586 patients who underwent gastrectomy for GC at Osaka Metropolitan University Hospital. CLDN18.2 expression was assessed by immunohistochemistry and classified as high or low according to staining intensity and percentage of positive cells. Associations between CLDN18.2 expression and clinicopathological features were evaluated. Overall survival (OS) was analyzed using Kaplan–Meier and Cox proportional hazards models. In addition, a systematic review of the literature was conducted, and meta-analysis was performed to assess the prognostic impact of CLDN18.2 expression. Results: CLDN18.2 expression was predominantly localized to the cancer cell membrane. There was no significant correlation between CLDN18.2 expression and clinicopathological characteristics. In the entire cohort, CLDN18.2 expression was not significantly associated with OS (log-rank p=0.669). However, subgroup analysis revealed a trend toward worse OS in patients with diffuse-type histology and high CLDN18.2 expression compared to those with low expression (log-rank p=0.092). The meta-analysis, including five eligible studies with over 1,000 patients, demonstrated no significant prognostic effect of CLDN18.2 on survival in resected GC (HR=0.892, 95%CI 0.71-1.13). Conclusions: Although CLDN18.2 expression was not a significant independent prognostic factor overall, diffuse-type GC patients with high CLDN18.2 expression tended to have worse survival.