title: Clinical application of the biomarkers for the selection of adjuvant chemotherapy in pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  For the establishment of personalized therapy, we investigated biomarkers that can contribute to the selection of adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  Between 2005 and 2014, of 141 consecutive patients with PDAC who underwent R0 or R1 resection, 61 patients given gemcitabine and 31 patients given S-1 as adjuvant therapy were enrolled. We evaluated the correlation between treatment outcomes and the expressions of intratumoral human antigen R (HuR), human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD).
  
  
  RESULTS
  There were no significant differences in clinicopathological features between the gemcitabine and S-1 groups. Among those with high HuR expression and high hENT1 expression, the disease-free survival (DFS) was significantly higher with gemcitabine than with S-1 (MST: 26.2 vs. 11.8 months, P = 0.024; 20.2 vs. 10.2 months, P = 0.029, respectively). Moreover, high HuR/hENT1 (high HuR or high hENT1) was significantly associated with better outcome for gemcitabine (HR for DFS: 0.43, P = 0.027) and low HuR/hENT1 was significantly associated with worse outcome for gemcitabine (HR for DFS: 2.24, P = 0.021). TS and DPD expression levels were not informative in this examination.
  
  
  CONCLUSIONS
  HuR and hENT1 were good candidates as selective biomarkers and this study's concept could contribute to personalized therapy for PDAC patients.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Oba
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. d-ban.msrg@tmd.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ban
authors.affiliation: Department of Pathology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kirimura
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Akahoshi
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mitsunori
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsumura
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ochiai
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kudo
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Tanabe
authors.initials: T
authors.lastname: Minoru
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage*; D010180:Pancreatectomy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018579:Patient Selection; D057285:Precision Medicine; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage*; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine
keywords: Biomarker; HuR; Pancreatic ductal adenocarcinoma; Personalized therapy; hENT1