Expression of Claudin-18.2 in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis

Claudin-18.2 (CLDN18.2), a tight junction protein, has emerged as a promising molecular target in gastrointestinal cancers. However, its expression pattern and clinicopathological relevance in pancreatic ductal adenocarcinoma (PDAC) remain unclear.

To assess the prevalence, tumor-specific, and clinicopathological associations of CLDN18.2 expression in PDAC, and to identify sources of heterogeneity to clarify its value as a therapeutic target.

A systematic search across six major databases was conducted from inception to August 2025 in accordance with PRISMA guidelines. Included studies evaluated CLDN18.2 expression in adult PDAC using defined immunohistochemistry protocols. Random-effects models estimated pooled prevalence and odds ratios (ORs), with subgroup analyses exploring heterogeneity.

Sixteen studies including 2,025 patients with PDAC were included. The pooled prevalence of CLDN18.2 expression was 51.60% (95% CI: 40.93-62.19), with substantial heterogeneity (I² = 95.4%). Expression varied significantly by antibody clone (p = 0.0006), but not by geographic regions. CLDN18.2 expression was highly specific to neoplastic tissue (OR = 102.40; 95% CI: 35.50-295.38). No significant associations were identified with sex, tumor location, T-stage, N-stage, or metastatic status. However, expression was significantly lower in poorly differentiated tumors (G3 vs. G1/G2: OR = 0.37; 95% CI: 0.20-0.70).

CLDN18.2 is frequently expressed in PDAC and shows high tumor specificity, supporting its relevance as a therapeutic biomarker. Despite assay variability, even under stringent clinical trial criteria, a meaningful subset of patients may qualify for CLDN18.2-targeted therapy. These findings highlight the need for standardized testing and further clinical evaluation of CLDN18.2-directed strategies in PDAC.