Combined Analysis of Dihydropyrimidine Dehydrogenase and Human Equilibrative Nucleoside Transporter 1 Expression Predicts Survival of Pancreatic Carcinoma Patients Treated with Adjuvant Gemcitabine Plus S-1 Chemotherapy after Surgical Resection

Abstract

Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival in some patients, the effectiveness varies by individual, and the results remain unsatisfying. The aim of this study was to investigate whether intratumoral dihydropyrimidine dehydrogenase (DPD) and human equilibrative nucleoside transporter 1 (hENT1) expression can predict the survival of PDAC patients treated with adjuvant gemcitabine plus S-1 (GEM+S-1) chemotherapy. Intratumoral DPD and hENT1 expression were examined by immunohistochemistry in 86 PDAC patients who received adjuvant GEM+S-1 chemotherapy after surgical resection (all R0 or R1). Relationships between clinicopathologic factors, including DPD and hENT1 expression, and disease-free or overall survival were evaluated by univariate and multivariate analyses. DPD and hENT1 expression had no significant relationship with any other clinicopathologic factors. A multivariate disease-free survival analysis revealed that lymph node metastasis (hazard ratio [HR], 2.90: 95% confidence interval [CI], 1.51-5.90; P = 0.001), DPD expression (HR 2.47; 95% CI 1.37-4.44; P = 0.003), and hENT1 expression (HR 2.55; 95% CI 1.37-4.64; P = 0.004) as independent factors. Multivariate overall survival analysis also identified pT factor (HR 3.47; 95% CI 1.08-15.8; P = 0.03), lymph node metastasis (HR 2.08; 95% CI 1.01-4.57; P = 0.04), DPD expression (HR 1.98; 95% CI 1.06-3.71; P = 0.03), and hENT1 expression (HR 2.18; 95% CI 1.10-4.19; P = 0.02) as independent factors. Combined analysis of DPD and hENT1 expression predicts the survival of PDAC patients treated with adjuvant GEM+S-1 chemotherapy.