Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis

• Published in: Journal of gastroenterology 2011-05, Vol.46 (5), p.577-585
• Main Authors: Umemura, Hiroshi, Togawa, Akira, Sogawa, Kazuyuki, Satoh, Mamoru, Mogushi, Kaoru, Nishimura, Motoi, Matsushita, Kazuyuki, Tanaka, Hiroshi, Takizawa, Hirotaka, Kodera, Yoshio, Nomura, Fumio
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Adenocarcinoma - diagnosis; Adenocarcinoma - pathology; Aged; Area Under Curve; Biomarkers, Tumor - blood; Biomarkers, Tumor - metabolism; Cancer; Case-Control Studies; CEA (Oncology); Colorectal Surgery; Comparative analysis; Diagnosis; Early Detection of Cancer - methods; Female; Gastroenterology; Hepatology; Humans; Ionization; Kininogen, High-Molecular-Weight - blood; Kininogen, High-Molecular-Weight - metabolism; Male; Mass spectrometry; Mass Spectrometry - methods; Medicine; Medicine & Public Health; Middle Aged; Molecular Weight; Neoplasm Proteins - analysis; Oncology, Experimental; Original Article—Alimentary Tract; Peptides; Proteases; Proteome - analysis; Proteomics - methods; ROC Curve; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Stomach cancer; Stomach Neoplasms - blood; Stomach Neoplasms - diagnosis; Stomach Neoplasms - pathology; Surgical Oncology
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-010-0369-3

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.