title: Prognostic predictive values of gemcitabine sensitivity-related gene products for unresectable or recurrent biliary tract cancer treated with gemcitabine alone.
abstract: BACKGROUND
  Gemcitabine is a pyrimidine nucleoside analog that is a commonly used chemotherapeutic agent for unresectable or recurrent biliary tract cancer (BTC). Several molecules involved in gemcitabine metabolism, including human equilibrative nucleoside transporter (hENT1), deoxycytidine kinase (dCK), and ribonucleotide reductase subunit M1 (RRM1), have been investigated as predictive biomarkers of gemcitabine efficacy, mostly in pancreatic cancer. The aim of this study is to clarify which biomarker is the most reliable among hENT1, dCK, and RRM1 to predict survival in patients with advanced BTC treated with gemcitabine alone.
  
  
  METHODS
  The analysis was performed on samples from 28 patients with unresectable or recurrent BTC who were treated with gemcitabine alone as first-line therapy. The starting date of overall survival (OS) and progression-free survival (PFS) was defined as the date of first treatment with gemcitabine. Intratumoral hENT1, dCK, and RRM1 expressions were examined by immunohistochemistry.
  
  
  RESULTS
  The expressions of hENT1, dCK, and RRM1 had no significant relationships with age, gender, primary tumor site, recurrence/unresectable, or histological type. Among the three molecules, only hENT1 expression was a significant factor affecting OS and PFS in univariate analysis; OS was 11.4 months for high hENT1 expression versus 5.7 months for low, P = 0.0057; PFS was 7.7 months for high versus 2.5 months for low, P = 0.0065. Multivariate analyses also identified hENT1 expression as an independent predictive factor for OS.
  
  
  CONCLUSIONS
  hENT1 is the most reliable predictive marker of survival in patients with advanced BTC treated with gemcitabine.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Murata
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Amano
authors.forename: Nobuya
authors.initials: N
authors.lastname: Yamada
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yashiro
authors.forename: Bunzo
authors.initials: B
authors.lastname: Nakata
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003842:Deoxycytidine Kinase / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D009367:Neoplasm Staging; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D033721:Equilibrative Nucleoside Transporter 1; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D003842:Deoxycytidine Kinase; D000093542:Gemcitabine