title: Serum REG4 level is a predictive biomarker for the response to preoperative chemoradiotherapy in patients with pancreatic cancer.
abstract: OBJECTIVE
  Preoperative chemoradiotherapy is one of the key strategies for the improvement of survival in pancreatic cancer; however, no method to predict the response has yet been established. The aim of this study was to prospectively evaluate the predictive value of REG4, a new member of the regenerating (REG) islet-derived family of proteins.
  
  
  METHODS
  Stably REG4-expressing cells were established from a pancreatic cancer cell line and exposed in vitro to gamma-ray or gemcitabine to investigate the relevance of REG4 to the resistance to chemotherapy or radiotherapy. In 23 patients with resectable pancreatic cancer, the serum concentration of REG4 was measured before preoperative chemoradiotherapy, and the histologic response was evaluated after the surgery.
  
  
  RESULTS
  A 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and fluorescence activated cell scanning (FACS) revealed that REG4-overexpressing cells were resistant to gamma-radiation but showed a modest resistance to gemcitabine. The patients with a higher REG4 level, but not carcinoembryonic antigen or CA-19-9, showed an unfavorable histologic response to chemoradiotherapy (Spearman, rho = 0.439, P = 0.039). The patients showing a higher REG4 level experienced local recurrence postoperatively.
  
  
  CONCLUSIONS
  These data demonstrated in vitro and in vivo that REG4 protein overexpression was associated with an unfavorable response to preoperative chemoradiotherapy. REG4 can clinically be used as a predictive biomarker.
authors: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. hidetoshi-eguchi@nifty.com
authors: Hidetoshi
authors: H
authors: Eguchi
authors: Osamu
authors: O
authors: Ishikawa
authors: Hiroaki
authors: H
authors: Ohigashi
authors: Hidenori
authors: H
authors: Takahashi
authors: Masahiko
authors: M
authors: Yano
authors: Kinji
authors: K
authors: Nishiyama
authors: Yasuhiko
authors: Y
authors: Tomita
authors: Rie
authors: R
authors: Uehara
authors: Akio
authors: A
authors: Takehara
authors: Yusuke
authors: Y
authors: Nakamura
authors: Hidewaki
authors: H
authors: Nakagawa
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D005720:Gamma Rays; D006801:Humans; D037181:Lectins, C-Type / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D000073718:Pancreatitis-Associated Proteins; D011237:Predictive Value of Tests; D018714:Radiotherapy, Adjuvant / Q000379:methods; D014162:Transfection; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C428528:REG4 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine