title: Concurrent analysis of human equilibrative nucleoside transporter 1 and ribonucleotide reductase subunit 1 expression increases predictive value for prognosis in cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy.
abstract: BACKGROUND
  The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC).
  
  
  METHODS
  Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated.
  
  
  RESULTS
  High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced.
  
  
  CONCLUSIONS
  Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC.
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Uemura
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sudo
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sueda
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; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D003430:Cross-Sectional Studies; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D000093542:Gemcitabine