title: Human equilibrative nucleoside transporter 1 expression is a strong independent prognostic factor in UICC T3-T4 pancreatic cancer patients treated with preoperative gemcitabine-based chemoradiotherapy.
abstract: OBJECTIVE
  We aimed to determine the relationship between the intratumoral expression of human equilibrative nucleoside transporter (hENT1), the main gemcitabine transporter into cells, and the outcome of gemcitabine-based chemoradiotherapy (Gem-CRT) in patients with International Union Against Cancer (UICC) T3-T4 pancreatic adenocarcinoma.
  
  
  METHODS
  The expressions of hENT1, thymidylate synthase (TS), and dihydropyrimidine dehydrogenase were immunohistochemically analyzed using the resected specimens from 55 patients (T3, 38 and T4, 17) who had received curative-intent resection after Gem-CRT.
  
  
  RESULTS
  The status of hENT1 expression (positive in 39 and negative in 16) was significantly associated with "clinical efficacy" (defined as more than 50% reduction of the serum carbohydrate antigen [CA] 19-9 level with stable disease [SD] or partial response [PR] according to the Response Evaluation Criteria in Solid Tumors [RECIST]) for Gem-CRT. The 1- and 3-year overall survival (OS) rates were significantly higher in the positive hENT1 expression group (82.9, 39.5%) than in the negative expression group (42.9, 14.3%) (p = 0.0037). According to combination analysis of hENT1 and TS expressions, the 1- and 3-year OS rates were significantly higher in the positive-low combination (89.1, 51.0%) group than in the negative-high group (66.7, 0%) (p = 0.023). Multivariate analysis revealed that positive hENT1 expression and R0 resection were significant prognostic factors for OS.
  
  
  CONCLUSIONS
  The hENT1 expression in pancreatic adenocarcinoma strongly influences the outcome of preoperative Gem-CRT treatment. This biomarker could become a useful predictor of therapeutic effect for gemcitabine-based therapy in pancreatic cancer patients.
authors: Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan.
authors: Yasuhiro
authors: Y
authors: Murata
authors: Takashi
authors: T
authors: Hamada
authors: Masashi
authors: M
authors: Kishiwada
authors: Ichiro
authors: I
authors: Ohsawa
authors: Shugo
authors: S
authors: Mizuno
authors: Masanobu
authors: M
authors: Usui
authors: Hiroyuki
authors: H
authors: Sakurai
authors: Masami
authors: M
authors: Tabata
authors: Noriko
authors: N
authors: Ii
authors: Hiroyuki
authors: H
authors: Inoue
authors: Taizo
authors: T
authors: Shiraishi
authors: Shuji
authors: S
authors: Isaji
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D018395:CA-19-9 Antigen / Q000097:blood; D059186:Chemoradiotherapy, Adjuvant; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D015596:Nutrition Assessment; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D011379:Prognosis; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018395:CA-19-9 Antigen; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase