title: Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis.
abstract: BACKGROUND
  Serum biomarkers currently available for gastric cancers are not sufficiently sensitive and specific.
  
  
  METHODS
  We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to generate comparative peptide profiles of serum samples obtained from gastric cancer patients (n = 81) and age- and sex-matched healthy controls (n = 66).
  
  
  RESULTS
  Because of initial screening and further validation, we found that the intensities of a 2209 m/z MS peak were increased in the preoperative sera obtained from gastric cancer patients, and we identified this peak, a 2209 Da peptide, as a high molecular weight (HMW) kininogen fragment. Receiver operating characteristic analyses showed that the area under the curve (AUC) for the 2209 Da peptide (AUC = 0.715) was greater than those for conventional tumor markers (carcinoembryonic antigen AUC = 0.593, carbohydrate antigen 19-9 AUC = 0.527) used for the detection of stage I gastric cancers. Inverse correlations were observed between the levels of intact HMW kininogen and the 2209 Da peptide, suggesting that the upregulation of some protease activities is responsible for the overproduction of a kininogen fragment in gastric cancer patients.
  
  
  CONCLUSIONS
  Serum levels of the 2209 Da peptide identified in this study have a greater diagnostic ability than those of conventional tumor markers used for the early detection of gastric cancer.
authors.affiliation: Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba 260-8670, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Umemura
authors.forename: Akira
authors.initials: A
authors.lastname: Togawa
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sogawa
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.forename: Motoi
authors.initials: M
authors.lastname: Nishimura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsushita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Takizawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kodera
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D019679:Kininogen, High-Molecular-Weight / Q000097:blood / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000032:analysis; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013274:Stomach Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019679:Kininogen, High-Molecular-Weight; D009363:Neoplasm Proteins; D020543:Proteome