Journal
ONCOGENE
Volume 26, Issue 30, Pages 4383-4393Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210215
Keywords
reg IV; apoptosis; 5-fluorouracil; serum tumor marker; SAGE; gastric cancer
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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 signifi. cantly 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.
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