title: Combined analysis of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression is a powerful predictor of survival in patients with pancreatic carcinoma treated with adjuvant gemcitabine-based chemotherapy after operative resection.
abstract: BACKGROUND
  Although postoperative adjuvant chemotherapy for pancreatic carcinoma improves survival in some patients, its efficacy varies among individuals. The aim of this study was to determine the usefulness of intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) as predictive markers of the efficacy of adjuvant gemcitabine-based chemotherapy for pancreatic carcinoma after operative resection.
  
  
  METHODS
  The expression of intratumoral hENT1 and RRM1 was examined immunohistochemically in 109 patients with pancreatic carcinoma who received adjuvant gemcitabine-based chemotherapy after operative resection. Relationships between clinicopathologic factors, including hENT1 and RRM1 expression, and disease-free and overall survival (DFS and OS) were evaluated by univariate and multivariate analyses.
  
  
  RESULTS
  The 5-year DFS and OS rates for the 109 patients were 26% and 31%, respectively. In univariate analysis, both hENT1 and RRM1 expression were significantly associated with DFS (hENT1, P = .004; RRM1, P = .011) and OS (hENT1, P = .001; RRM1, P = .040). In multivariate analysis, both were independent factors for DFS (hENT1, P = .001; RRM1, P = .009) and OS (hENT1, P = .001, RRM1, P = .019). Evaluation of the combination analysis of both was also identified as a powerful independent predictor of DFS (P < .001) and OS (P < .001).
  
  
  CONCLUSIONS
  Expression of hENT1 and RRM1 is predictive of the efficacy of adjuvant gemcitabine-based chemotherapy for pancreatic carcinoma after operative resection. In addition, their combined analysis has greater predictive value than either factor alone.
authors.affiliation: Department of Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. naoyaman423@hiroshima-u.ac.jp
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Uemura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sudo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Naru
authors.initials: N
authors.lastname: Kondo
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D000093542:Gemcitabine