Human equilibrative nucleoside transporter 1 expression predicts survival of advanced cholangiocarcinoma patients treated with gemcitabine-based adjuvant chemotherapy after surgical resection

Ann Surg. 2012 Aug;256(2):288-96. doi: 10.1097/SLA.0b013e3182536a42.

Abstract

Objective: The aim of this study was to evaluate whether intratumoral human equilibrative nucleoside transporter 1 (hENT1) expression can predict the survival of advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection.

Background: There have been no reports concerning a useful predictive biomarker in patients with cholangiocarcinoma treated with adjuvant gemcitabine chemotherapy.

Methods: Intratumoral hENT1 expression was investigated immunohistochemically in 105 patients with resected advanced cholangiocarcinoma. Relationships between intratumoral hENT1 expression and clinicopathological factors were evaluated by univariate and multivariate analyses. This study was a retrospective analysis on retrospectively collected tissue and data.

Results: Fifty-one patients received AGC, and 54 did not. High and low intratumoral hENT1 expression was found in 74 (70%) and 31 patients (30%), respectively. There were no significant differences in clinicopathological factors between patients with high hENT1 expression and those with low hENT1 expression. Survival patients with high hENT1 expression were significantly better than those with low hENT1 expression among patients who received AGC (P = 0.008), but not among patients who did not (P = 0.894). Moreover, a significant difference in survival between patients who received AGC and those who did not was observed among patients with high hENT1 expression (P = 0.002), but not among patients with low hENT1 expression (P = 0.525). Intratumoral hENT1 expression was only an independent predictive factor for patients treated with AGC by multivariate analysis (P = 0.027).

Conclusions: Intratumoral hENT1 expression may be a potent predictive marker for advanced cholangiocarcinoma patients treated with AGC.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Bile Duct Neoplasms / drug therapy
  • Bile Duct Neoplasms / mortality*
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / surgery
  • Bile Ducts, Intrahepatic*
  • Cholangiocarcinoma / drug therapy
  • Cholangiocarcinoma / mortality*
  • Cholangiocarcinoma / pathology
  • Cholangiocarcinoma / surgery
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Equilibrative Nucleoside Transporter 1 / metabolism*
  • Female
  • Gemcitabine
  • Hepatectomy
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Pancreaticoduodenectomy
  • Prognosis
  • Survival Analysis

Substances

  • Antimetabolites, Antineoplastic
  • Equilibrative Nucleoside Transporter 1
  • SLC29A1 protein, human
  • Deoxycytidine
  • Gemcitabine