title: Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC).
abstract: OBJECTIVE
  Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients' outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-based therapy.
  
  
  METHODS
  The immunohistochemistry analysis was performed on samples from thirty-one patients with unresectable biliary tract cancer (BTC) consecutively treated with first line gemcitabine-based regimens.
  
  
  RESULTS
  Positive hENT1 staining patients were 21 (67.7%); negative hENT1 staining patients were 10 (32.3%). Statistical analysis revealed no association between baseline characteristics, toxicities and tumor response to gemcitabine and hENT1 levels. In the univariate analysis, HENT1 expression was significantly correlated with time to progression (TTP) (p=0.0394; HR 2.902, 95%CI 1.053-7.996). The median TTP was 6.33 versus 2.83 months, respectively in patients with positive versus negative hENT1 staining. Moreover, patients with positive hENT1 expression showed a longer median overall survival when compared with patients with low hENT1 expression (14 versus 7 months, respectively), but this difference did not reach the statistical significance (p=0.128).
  
  
  CONCLUSIONS
  Therefore, hENT1 may be a relevant predictive marker of benefit from gemcitabine-based therapies in patients with advanced BTC.
authors.affiliation: Medical Oncology, University Campus Bio-Medico, Rome, Italy. d.santini@unicampus.it
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Gaia
authors.initials: G
authors.lastname: Schiavon
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Carol E
authors.initials: CE
authors.lastname: Cass
authors.forename: Enrico
authors.initials: E
authors.lastname: Vasile
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Manazza
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Catalano
authors.forename: Giacomo Giulio
authors.initials: GG
authors.lastname: Baldi
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.forename: Alice
authors.initials: A
authors.lastname: Giacobino
authors.forename: Luigi
authors.initials: L
authors.lastname: Chiusa
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: John
authors.initials: J
authors.lastname: Mackey
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D033721:Equilibrative Nucleoside Transporter 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine