Prognostic Value of Claudin 18.2, Isocitrate Dehydrogenase-1, and Neutrophil-to-Lymphocyte Ratio in Unresectable Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with limited treatment options. Identifying reliable prognostic biomarkers is crucial for risk stratification and therapeutic decision-making. This study investigates the prognostic significance of Claudin 18.2 (CLDN18.2), isocitrate dehydrogenase-1 (IDH1) expression, and the neutrophil-to-lymphocyte ratio (NLR) in patients with unresectable PDAC receiving first-line chemotherapy. This retrospective, single-center study included 72 patients with histologically confirmed unresectable PDAC treated with either FOLFIRINOX (59.7%) or gemcitabine plus nab-paclitaxel (40.3%). Immunohistochemistry was performed to assess CLDN18.2 and IDH1 expression, while NLR was calculated from pre-treatment blood counts. Univariable and multivariable analyses were conducted to evaluate predictors of progression-free survival (PFS) and overall survival (OS). CLDN18.2 and IDH1 were positively expressed in 18.1% and 2.8% of patients, respectively, while 56.9% had elevated NLR (>3.22). The median PFS was 7.1 months (95% CI: 4.2–9.9), and the median OS was 9.7 months (95% CI: 8.5–10.8). Multivariable analysis identified negative CLDN18.2 expression (HR = 0.38, 95% CI: 0.18–0.81, p = 0.013), positive IDH1 expression (HR = 0.68, 95% CI: 0.19–0.72, p = 0.039), and high NLR (HR = 1.92, 95% CI: 1.03–3.56, p = 0.038) as independent predictors of poorer OS. No independent predictors of PFS were identified. CLDN18.2 and IDH1 expression, along with NLR, are independent prognostic markers for OS in patients with unresectable PDAC undergoing first-line chemotherapy. These biomarkers may facilitate risk stratification and guide personalized treatment strategies. Further prospective validation is warranted to confirm their clinical utility.