The prognostic value of CLDN18.2 expression in pancreatic ductal adenocarcinoma: a systematic review and individual patient data meta-analysis.

Pancreatic ductal adenocarcinoma (PDAC) is the most common malignant tumor of the exocrine pancreas. Due to the limited treatment options currently available and the challenges in timely and accurate screening, most patients experience rapid disease progression following initial diagnosis. CLDN18.2, an isoform of claudin-18, is normally expressed in gastric tissues but can be ectopically expressed in PDAC. This biomarker remains underexplored in the context of PDAC, and its association with patient prognosis is not yet fully understood. We conducted a systematic search in PubMed, Embase, Web of Science, and Cochrane for studies addressing the correlation between CLDN18.2 and the prognosis of patients diagnosed with PDAC. We analyzed the hazard ratio (HR) and odds ratio (OR), with 95% confidence intervals (CIs). P-values ≤ 0.05 were considered statistically significant. All statistical analyses were performed using RStudio, version 4.2.3. A total of six studies were included, encompassing 972 patients with PDAC, of whom 424 (43.5%) exhibited CLDN18.2 expression. The cohort consisted of 526 (54%) male and 446 (46%) female patients. The median overall survival (OS) was 19.89 months (95% CI: 17.86-22.94) in the CLDN18.2-positive group and 18.02 months (95% CI: 15.90-19.96) in the CLDN18.2-negative group. In a pooled analysis of three studies including resected PDAC patients, CLDN18.2 positivity was significantly associated with improved overall survival compared to CLDN18.2 negativity (HR = 0.74; 95% CI: 0.60-0.89; p = 0.0025). In the survival analysis, patients with positive CLDN18.2 status had better OS (HR: 0.77; 95% CI: 0.67-0.89). Among Asian patients, CLDN18.2 positivity was also associated with longer OS (HR: 0.77; 95% CI: 0.64-0.93), whereas in non-Asian patients, there appeared to be no significant difference between the two groups (HR: 0.84; 95% CI: 0.68-1.04). Our findings establish CLDN18.2 as a prognostic biomarker in patients diagnosed with PDAC. CLDN18.2 positivity is associated with improved OS, particularly in the Asian population. Although non-Asian patients also demonstrated a trend toward improved survival, the difference was not statistically significant. Further studies are needed to explore the therapeutic and clinical implications of CLDN18.2 expression in diverse populations worldwide.