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  • Oncogenomics
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Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer

Oncogene volume 25, pages 2546–2557 (2006)Cite this article

Abstract

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue will be useful molecular markers for diagnosis and may also be good therapeutic targets. However, little is known about cancer-specific genes, at least in GC. In this study, we searched for GC-specific genes by serial analysis of gene expression (SAGE) data analysis and quantitative reverse transcription (RT)–PCR. Comparing GC SAGE libraries with those of various normal tissues in the SAGEmap database, we identified 54 candidate GC-specific genes. Quantitative RT–PCR analysis of these candidates revealed that APin protein (APIN), taxol resistance-associated gene 3 (TRAG3), cytochrome P450, family 2, subfamily W, polypeptide 1 (CYP2W1), melanoma inhibitory activity (MIA), matrix metalloproteinase-10 (MMP-10), dickkopf homolog 4 (DKK4), GW112, regenerating islet-derived family, member 4 (REGIV), and HORMA domain-containing 1 (HORMAD1) were expressed much more highly in GC than in 14 kinds of normal tissues. Immunohistochemical staining for MIA, MMP-10, and DKK4 was found in 47 (31.1%), 68 (45.0%), and two (1.3%) of 151 GCs, respectively, and staining for both MIA and MMP-10 was correlated with poor prognosis in advanced GC (P=0.0001 and 0.0141, respectively). Moreover, enzyme-linked immunosorbent assay showed high levels of MMP-10 (65/69, 94.2%) in serum samples from patients with GC. Levels of MIA were raised in a small proportion of serum samples from patients with GC (4/69, 5.8%). In Boyden chamber invasion assays, MIA-transfected GC cells were up to three times more invasive than cells transfected with empty vector. Taken together, these results suggest that MMP-10 is a good marker for the detection of GC and that MIA and MMP-10 are prognostic factors for GC. As expression of MIA and MMP-10 is narrowly restricted in cancer, these two molecules may be good therapeutic targets for GC.

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Acknowledgements

We thank M Takatani 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

    P P Aung, N Oue, Y Mitani, H Nakayama & W Yasui

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

    K Yoshida

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

    T Noguchi

  4. Institute of Pathology, University of Regensburg, Regensburg, Germany

    A K Bosserhoff

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Correspondence to W Yasui.

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Aung, P., Oue, N., Mitani, Y. et al. Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer. Oncogene 25, 2546–2557 (2006). https://doi.org/10.1038/sj.onc.1209279

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