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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.

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Acknowledgments

We thank Masumi Ishibashi and Satomi Tojo Nishimura for their technical assistance. We also thank members of the clinical laboratory staff of Kimitsu Chuo Hospital and PortSquare Kashiwado Clinic for collecting serum samples. This work was supported in part by Grants-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (Nos. 19390154 and 20790411).

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Correspondence to Fumio Nomura.

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Umemura, H., Togawa, A., Sogawa, K. et al. Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis. J Gastroenterol 46, 577–585 (2011). https://doi.org/10.1007/s00535-010-0369-3

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  • DOI: https://doi.org/10.1007/s00535-010-0369-3

Keywords

  • Gastric adenocarcinoma
  • MALDI-TOF MS
  • Proteomics
  • Serum biomarkers
  • High molecular weight kininogen