Claudin 18.2, IDH1, and neutrophil-to-lymphocyte ratio as prognostic biomarkers in unresectable pancreatic ductal adenocarcinoma receiving first-line chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with few effective treatment options. 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 undergoing first-line chemotherapy. This single-center retrospective analysis utilized prospectively collected data from 72 patients treated with FOLFIRINOX (59.7%) or gemcitabine plus nab-paclitaxel (40.3%). CLDN18.2 and IDH1 expression levels were evaluated through immunohistochemistry, while NLR was calculated from pretreatment blood counts. Survival analyses were conducted using univariable and multivariable Cox regression models. CLDN18.2 positivity was found in 18.1% of patients, and IDH1 positivity was observed in 2.8%. Additionally, an elevated NLR (>3.22) was present in 56.9% of patients. The median progression-free survival (PFS) and overall survival (OS) were 7.1 months (95% CI: 4.2-9.9) and 9.7 months (95% CI: 8.5-10.8), respectively. In the multivariable analysis, CLDN18.2 expression, IDH1 expression, and NLR were significantly associated with OS, whereas no consistent associations were found for PFS. Effect estimates include corresponding 95% confidence intervals. These findings indicate the potential prognostic value of integrating molecular and systemic biomarkers in unresectable PDAC. However, due to the retrospective design and limited sample size, these results should be regarded as hypothesis-generating and necessitate validation in larger, independent cohorts prior to clinical implementation.