Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy.
Regenerating gene family, member 4 (Reg IV), a secreted protein, is overexpressed in several cancers, including gastric cancer (GC). In the present study, we measured Reg IV levels in sera from patients with GC by enzyme-linked immunosorbent assay. We also examined the effect of forced Reg IV expression on the apoptotic susceptibility to 5-fluorouracil (5-FU). Forced expression of Reg IV inhibited 5-FU-induced apoptosis. Induction of Bcl-2 and dihydropyrimidine dehydrogenase was involved in inhibition of apoptosis. Among 36 GC patients treated with a combination chemotherapy of low-dose 5-FU and cisplatin, all 14 Reg IV-positive patients showed no change or disease progression. The serum Reg IV concentration was similar between healthy individuals (mean+/-s.e., 0.52+/-0.05 ng/ml) and patients with chronic-active gastritis (0.36+/-0.09 ng/ml). However, the serum Reg IV concentration in presurgical GC patients was significantly elevated (1.96+/-0.17 ng/ml), even at stage I. The diagnostic sensitivity of serum Reg IV (36.1%) was superior to that of serum carcinoembryonic antigen (11.5%) or carbohydrate antigen 19-9 (13.1%). These results indicate that expression of Reg IV is a marker for prediction of resistance to 5-FU-based chemotherapy in patients with GC. Serum Reg IV represents a novel biomarker for GC.
Mitani
Y
Y
Department of Molecular Pathology, Hiroshima University, Graduate School of Biomedical Sciences, Hiroshima, Japan.
Oue
N
N
Matsumura
S
S
Yoshida
K
K
Noguchi
T
T
Ito
M
M
Tanaka
S
S
Kuniyasu
H
H
Kamata
N
N
Yasui
W
W
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000032:analysis; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D037181:Lectins, C-Type / Q000032:analysis / Q000097:blood*; D000073718:Pancreatitis-Associated Proteins; D013274:Stomach Neoplasms / Q000097:blood* / Q000188:drug therapy*
D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C428528:REG4 protein, human; D002945:Cisplatin; D005472:Fluorouracil