title: Soluble c-Met protein as a susceptible biomarker for gastric cancer risk: A nested case-control study within the Korean Multicenter Cancer Cohort.
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.
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Yang
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Yang
authors.forename: Jungkon
authors.initials: J
authors.lastname: Kim
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Ma
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Cho
authors.forename: Kwang-Pil
authors.initials: KP
authors.lastname: Ko
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.forename: Bo Youl
authors.initials: BY
authors.lastname: Choi
authors.forename: Hyun Ja
authors.initials: HJ
authors.lastname: Kim
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Han
authors.forename: Chang Soo
authors.initials: CS
authors.lastname: Eun
authors.forename: Kyu Sang
authors.initials: KS
authors.lastname: Song
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Soung-Hoon
authors.initials: SH
authors.lastname: Chang
authors.forename: Hai-Rim
authors.initials: HR
authors.lastname: Shin
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
mesh_terms: D000942:Antigens, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D016481:Helicobacter Infections / Q000097:blood* / Q000209:etiology / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000097:blood*; D012372:ROC Curve; D013274:Stomach Neoplasms / Q000097:blood* / Q000209:etiology / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D014408:Biomarkers, Tumor; C080866:cagA protein, Helicobacter pylori; D019859:Proto-Oncogene Proteins c-met