Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy

Mitani Yoshitsugu

Oue Naohide

Matsumura Shunji

Yoshida Kazuhiro

Noguchi Tsuyoshi

Ito Masanori

Tanaka Shinji

Kuniyasu Hiroki

Kamata Nobuyuki

Yasui Wataru

Oncogene

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.

Reg IV

apoptosis

5-fluorouracil

serum tumor marker

SAGE

gastric cancer

Medical sciences [ 490 ]

eng

Nature Publishing Group

Copyright (c) 2007 Nature Publishing Group.

[ISSN] 0950-9232

[DOI] 10.1038/sj.onc.1210215

[PMID] 17237819

[NCID] AA10687380

[DOI] http://dx.doi.org/10.1038/sj.onc.1210215