title: A meta-analysis of gemcitabine biomarkers in patients with pancreaticobiliary cancers.
abstract: OBJECTIVE
  The objective of this study was to summarize all clinical studies evaluating the prognostic role of gemcitabine (GEM) metabolic genes in pancreaticobiliary (PB) cancer patients receiving GEM therapy in the neoadjuvant, adjuvant, or palliative settings.
  
  
  METHODS
  Meta-analyses were performed to calculate the pooled hazard ratios for each gene by each clinical outcome (overall survival [OS], disease-free survival [DFS], and progression-free survival) using a random-effects approach.
  
  
  RESULTS
  The search strategy identified 16 eligible studies, composed of 632 PB patients total, with moderate quality. Compared with low expression, pooled hazard ratios for OS of hENT1, dCK, RRM1, RRM2, and DPD were 0.37 (95% confidence interval [CI], 0.28-0.47), 0.40 (95% CI, 0.20-0.80), 2.21 (95% CI, 1.12-4.36), 2.13 (95% CI, 1.00-4.52), and 1.91 (95% CI, 1.16-3.17), respectively. A similar trend was observed for each of these biomarkers in DFS and progression-free survival prognostication. Subgroup analyses for hENT1 showed a comparable survival correlation in the adjuvant and palliative settings.
  
  
  CONCLUSIONS
  High expression of hENT1 in PB cancer patients receiving GEM-based adjuvant therapy is associated with improved OS and DFS and may be the best examined prognostic marker to date. Evidence for other biomarkers is limited by a small number of publications investigating these markers.
authors.affiliation: From the *Division of General Surgery, Department of Surgery, †Department of Statistics, ‡Jonsson Comprehensive Cancer Center, §Department of Medicine, Division of Digestive Disease, ∥Institute for Molecular Medicine, and ¶Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA.
authors.forename: Christina H
authors.initials: CH
authors.lastname: Wei
authors.forename: Tristan R
authors.initials: TR
authors.lastname: Gorgan
authors.forename: David A
authors.initials: DA
authors.lastname: Elashoff
authors.forename: O Joe
authors.initials: OJ
authors.lastname: Hines
authors.forename: James J
authors.initials: JJ
authors.lastname: Farrell
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Donahue
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003842:Deoxycytidine Kinase / Q000235:genetics; D018572:Disease-Free Survival; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; 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; C093713:ribonucleotide reductase M2; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D003842:Deoxycytidine Kinase; D000093542:Gemcitabine