Soluble c-Met protein as a susceptible biomarker for gastric cancer risk: A nested case-control study within the Korean Multicenter Cancer Cohort
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- Soluble c-Met protein as a susceptible biomarker for gastric cancer risk: A nested case-control study within the Korean Multicenter Cancer Cohort
- J J Yang; J H Yang; J Kim; S H Ma; L Y Cho; K P Ko; A Shin; B Y Choi; H J Kim; D S Han; C S Eun; K S Song; Yong Sung Kim; S H Chang; H R Shin; D Kang; K Y Yoo; S K Park
- Bibliographic Citation
- International Journal of Cancer, vol. 132, no. 9, pp. 2148-2156
- Publication Year
- 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. What's new Infection with Cag-A positive H. pylori is a major risk factor for gastric cancer. Certain genetic variants along the Cag-A signaling pathway influence this risk, and one of these genes is the c-Met protein. This protein also has a soluble form that can be easily measured in plasma. In this study, the authors investigated soluble c-Met as a biomarker for gastric cancer. They compared the plasma concentration c-Met between 290 sets of gastric cancer cases and matched controls. Protein levels were lower in cases than controls, and in fact, the levels decreased as the onset of cancer drew nearer, suggesting a protective effect conferred by the circulating c-Met.
- biomarkerCagA-related genesgastric cancersoluble c-Met protein
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