title: Human equilibrative nucleoside transporter 1 (hENT1) expression is a potential predictive tool for response to gemcitabine in patients with advanced cholangiocarcinoma.
abstract: BACKGROUND
  Cholangiocarcinoma (CC) is a rare cancer of the liver. Surgery offers the only chance for cure. When surgery is unfeasible, chemotherapy is the backbone of treatment. The combined administration of cisplatin and gemcitabine is considered standard of care. Human equilibrative nucleoside transporter 1 (hENT1) is the major transporter responsible for gemcitabine uptake into cells. hENT1 expression is associated with an increased survival for patients receiving gemcitabine after pancreatic cancer surgery, suggesting that hENT1 is predictive of response to gemcitabine.
  
  
  OBJECTIVE
  To determine whether there is a correlation between the expression of hENT1 and disease outcome in CC.
  
  
  METHODS
  A retrospective study on 43 patients treated at our centre with a locally advanced or metastatic CC, who received first line treatment with gemcitabine, was performed.
  
  
  RESULTS
  For the whole population, median Progression Free Survival (PFS) and overall survival (OS) were 4.0 (95% Confidence Interval 2.7-5.3 months) and 10.0 months (95%CI 6.8-13.2 months), respectively. From the 26 samples available for hENT1 staining, 18 (69%) and 8 (31%) patients had high and low hENT1 immunostaining, respectively. The median PFS were 2.0 versus 6.0 months for low versus high staining respectively (p = 0.012). The median OS were 5.0 versus 11.0 months for low versus high staining, respectively (p = 0.036). On multivariate analysis, hENT1 expression was the single independent predictive factor associated with prolonged PFS (HR 0.35, p = 0.023) and OS (HR 0.41, p = 0.046).
  
  
  CONCLUSIONS
  In this study we show the potential of hENT1 expression as a predictor of outcome in CC treated with gemcitabine. Larger studies are necessary to confirm these promising results.
authors.affiliation: Gastroenterology Unit, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium. ivan.borbath@uclouvain.be
authors.forename: I
authors.initials: I
authors.lastname: Borbath
authors.forename: L
authors.initials: L
authors.lastname: Verbrugghe
authors.forename: R
authors.initials: R
authors.lastname: Lai
authors.forename: J F
authors.initials: JF
authors.lastname: Gigot
authors.forename: Y
authors.initials: Y
authors.lastname: Humblet
authors.forename: H
authors.initials: H
authors.lastname: Piessevaux
authors.forename: C
authors.initials: C
authors.lastname: Sempoux
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; D003841:Deoxycytidine; D000093542:Gemcitabine