Soluble c‐Met protein as a susceptible biomarker for gastric cancer risk: A nested case‐control study within the Korean Multicenter Cancer Cohort
Open Access
- 24 September 2012
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 132 (9), 2148-2156
- https://doi.org/10.1002/ijc.27861
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.This publication has 18 references indexed in Scilit:
- Genetic Susceptibility on CagA-Interacting Molecules and Gene-Environment Interaction with Phytoestrogens: A Putative Risk Factor for Gastric CancerPLOS ONE, 2012
- Oncogenic CagA Promotes Gastric Cancer Risk via Activating ERK Signaling Pathways: A Nested Case-Control StudyPLOS ONE, 2011
- Small molecule c-Met kinase inhibitors: a review of recent patentsExpert Opinion on Therapeutic Patents, 2010
- Genetic factors associated with intestinal metaplasia in a high risk Singapore-Chinese population: a cohort studyBMC Gastroenterology, 2009
- Association between serum pepsinogens and polymorphismofPTPN11 encoding SHP-2 amongHelicobacter pylori seropositive JapaneseInternational Journal of Cancer, 2005
- Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic responseThe Journal of cell biology, 2003
- Vascular Origin of a Soluble Truncated Form of the Hepatocyte Growth Factor Receptor (c-met)Circulation Research, 2002
- Identification of the Hepatocyte Growth Factor Receptor As the c- met Proto-Oncogene ProductScience, 1991
- p145, a protein with associated tyrosine kinase activity in a human gastric carcinoma cell line.Molecular and Cellular Biology, 1988
- The human met oncogene is related to the tyrosine kinase oncogenesNature, 1985