Soluble c-Met protein as a susceptible biomarker for gastric cancer risk: A nested case-control study within the Korean Multicenter Cancer Cohort

Authors

  • Jae Jeong Yang,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Korea
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  • Ji Hyun Yang,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Korea
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  • Jungkon Kim,

    1. Risk Assessment Division, National Institute of Environmental Research, Incheon, Korea
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  • Seung Hyun Ma,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Korea
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  • Lisa Y. Cho,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Korea
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  • Kwang-Pil Ko,

    1. Department of Preventive Medicine, Graduate school of medicine, Gachon University, Incheon, Korea
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  • Aesun Shin,

    1. Molecular Epidemiology Branch, Research Institute, National Cancer Center, Goyang, Korea
    2. Cancer Registration and Statistics Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea
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  • Bo Youl Choi,

    1. Department of Preventive Medicine, Hanyang University College of Medicine, Seoul, Korea
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  • Hyun Ja Kim,

    1. Department of Preventive Medicine, Hanyang University College of Medicine, Seoul, Korea
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  • Dong Soo Han,

    1. Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
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  • Chang Soo Eun,

    1. Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
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  • Kyu Sang Song,

    1. Department of Pathology, Chungnam National University College of Medicine, Daejeon, Korea
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  • Yong Sung Kim,

    1. Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
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  • Soung-Hoon Chang,

    1. Department of Preventive Medicine, Konkuk University, Chungju, Korea
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  • Hai-Rim Shin,

    1. Cancer Registration and Statistics Branch, National Cancer Control Institute, National Cancer Center, Goyang, Korea
    2. Non Communicable Diseases and Health Promotion, World Health Organization, Western Pacific Regional Office, Manila, Philippines
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  • Daehee Kang,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Korea
    3. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
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  • Keun-Young Yoo,

    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
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  • Sue K. Park

    Corresponding author
    1. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
    2. Cancer Research Institute, Seoul National University, Seoul, Korea
    3. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
    • Department of Preventive Medicine, Seoul National University College of Medicine, 103 Yongon (Daehangno), Jongno-gu, Seoul, Republic of Korea
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    • Tel.: +82-2-740-8338, Fax: +82-2-747-4830


Abstract

This study was conducted to evaluate the relevance of the soluble form of c-Met protein, a truncated form of the c-Met membrane receptor involved in the CagA pathway, as a potential biomarker for gastric cancer. Among 290 gastric cancer case-control sets selected from the Korean Multicenter Cancer Cohort, the plasma concentrations of soluble c-Met protein were measured with enzyme-linked immunosorbent assays. Using analysis of variance and covariance models with age, sex, smoking, Helicobacter pylori infection, and CagA seropositivity, the mean concentrations of soluble c-Met protein between cases and controls were compared. To evaluate the association between gastric cancer and a c-Met protein level, odds ratios and 95% confidence intervals were estimated using conditional logistic regression models. Interactions between CagA-related genes and the soluble c-Met protein concentration were also investigated. The overall median plasma concentration of soluble c-Met among cases was significantly lower than those of controls (1.390 vs. 1.610 ng/mL, p < 0.0001). Closer to the onset of gastric cancer, the soluble c-Met protein level decreased linearly in a time-dependent manner (p for trend = 0.0002). The combined effects between the CagA-related genes and the soluble c-Met protein concentration significantly intensified risks for gastric cancer. Restricted analyses including cases that had been diagnosed within 1 year after entering the cohort had a fair degree of ability (area under the receiver operating characteristic curve of 0.73–0.77) to discriminate gastric cancer cases from normal controls. Our findings demonstrate the potential of the soluble form of c-Met protein as a novel biomarker for gastric cancer. The beneficial effects of a high soluble c-Met concentration in human plasma are strongly supported.

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