Serum REG4 level is a predictive biomarker for the response to preoperative chemoradiotherapy in patients with pancreatic cancer.
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.
Eguchi
Hidetoshi
H
Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. hidetoshi-eguchi@nifty.com
Ishikawa
Osamu
O
Ohigashi
Hiroaki
H
Takahashi
Hidenori
H
Yano
Masahiko
M
Nishiyama
Kinji
K
Tomita
Yasuhiko
Y
Uehara
Rie
R
Takehara
Akio
A
Nakamura
Yusuke
Y
Nakagawa
Hidewaki
H
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
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C428528:REG4 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine