title: 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: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Combined analysis of DPD and hENT1 expression predicts the survival of PDAC patients treated with adjuvant GEM+S-1 chemotherapy.
authors.affiliation: Division of Clinical Medical Science, Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. k-naru@par.odn.ne.jp
authors.forename: Naru
authors.initials: N
authors.lastname: Kondo
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Uemura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sudo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Nakashima
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D018572:Disease-Free Survival; D004338:Drug Combinations; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010094:Oxonic Acid / Q000008:administration & dosage; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D016577:Pancreaticoduodenectomy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D005641:Tegafur / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D004338:Drug Combinations; D033721:Equilibrative Nucleoside Transporter 1; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP); D000093542:Gemcitabine