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

Oncogene volume 26, pages 4383–4393 (2007)Cite this article

Abstract

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.

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Acknowledgements

We thank M Takatani and M Ikeda for excellent technical assistance and advice. This work was carried out with the kind cooperation of the Research Center for Molecular Medicine, Faculty of Medicine, Hiroshima University. We thank the Analysis Center of Life Science, Hiroshima University for the use of their facilities. This work was supported, in part, by Grants-in-Aid for Cancer Research from the Ministry of Education, Culture, Science, Sports and Technology of Japan, and from the Ministry of Health, Labor and Welfare of Japan.

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Authors and Affiliations

  1. Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan

    Y Mitani, N Oue, S Matsumura & W Yasui

  2. Department of Oral and Maxillofacial Surgery, Division of Cervico-Gnathostomatology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan

    Y Mitani & N Kamata

  3. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    K Yoshida

  4. Department of Oncological Science (Surgery II), Oita University Faculty of Medicine, Oita, Japan

    T Noguchi

  5. Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan

    M Ito & S Tanaka

  6. Department of Molecular Pathology, Nara Medical University, Kashihara, Japan

    H Kuniyasu

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  1. Y Mitani
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Correspondence to W Yasui.

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Mitani, Y., Oue, N., Matsumura, S. et al. Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy. Oncogene 26, 4383–4393 (2007). https://doi.org/10.1038/sj.onc.1210215

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  • DOI: https://doi.org/10.1038/sj.onc.1210215

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