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Comparison of serum trefoil factor 3 with the pepsinogen test for the screening of diffuse-type gastric cancer

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Abstract

Emerging data show that serum trefoil factor 3 (TFF3) alone and combined with the serum pepsinogen (PG) test can increase the diagnostic yield of gastric cancer. We aimed to evaluate the diagnostic value of serum TFF3 for the screening of gastric cancer in Korean patients, especially for the screening of the diffuse type of gastric cancer, and compared TFF3 to the serum PG test. We enrolled 25 healthy controls and 79 subjects with gastric cancer who underwent endoscopic resection or surgery from June 2006 to June 2015. Data about age, sex, histological type according to the Lauren classification, stage of gastric cancer, and status of H. pylori were collected. Serum levels of PG I and PG II were measured by the latex-enhanced turbidimetric immunoassay, and serum TFF3 levels were measured by enzyme-linked immunosorbent assay. The optimal cutoff value of serum TFF3 was ≥8.9 ng/mL to diagnose gastric cancer, with 73.4 % sensitivity and 92.0 % specificity, which were higher than those of the serum PG I/II ratio, with 69.6 % sensitivity and 68.0 % specificity. The optimal sensitivity and specificity of serum TFF3 for the diagnosis of diffuse-type gastric cancer were 68.0 and 92.0 %, respectively, which were lower than those for the diagnosis of intestinal-type gastric cancer (75.6 and 100 %, respectively). Serum TFF3 is a more stable and useful marker than the serum PG test for the screening of gastric cancer in Korean patients. Serum TFF3 showed good diagnostic power in detecting both intestinal- and diffuse-type gastric cancer although it showed decreased power in diffuse type.

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References

  1. Kim N, Jung HC. The role of serum pepsinogen in the detection of gastric cancer. Gut Liver. 2010;4(3):307–19. doi:10.5009/gnl.2010.4.3.307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Miki K. Gastric cancer screening using the serum pepsinogen test method. Gastric Cancer. 2006;9(4):245–53. doi:10.1007/s10120-006-0397-0.

    Article  PubMed  Google Scholar 

  3. Dinis-Ribeiro M, Yamaki G, Miki K, Costa-Pereira A, Matsukawa M, Kurihara M. Meta-analysis on the validity of pepsinogen test for gastric carcinoma, dysplasia or chronic atrophic gastritis screening. J Med Screen. 2004;11(3):141–7. doi:10.1258/0969141041732184.

    Article  CAS  PubMed  Google Scholar 

  4. Hattori Y, Tashiro H, Kawamoto T, Kodama Y. Sensitivity and specificity of mass screening for gastric cancer using the measurment of serum pepsinogens. Jpn J cancer Res Gann. 1995;86(12):1210–5.

    Article  CAS  PubMed  Google Scholar 

  5. Yoshihara M, Sumii K, Haruma K, Kiyohira K, Hattori N, Kitadai Y, et al. Correlation of ratio of serum pepsinogen I and II with prevalence of gastric cancer and adenoma in Japanese subjects. Am J Gastroenterol. 1998;93(7):1090–6. doi:10.1111/j.1572-0241.1998.00335.x.

    Article  CAS  PubMed  Google Scholar 

  6. Kang JM, Kim N, Yoo JY, Park YS, Lee DH, Kim HY, et al. The role of serum pepsinogen and gastrin test for the detection of gastric cancer in Korea. Helicobacter. 2008;13(2):146–56. doi:10.1111/j.1523-5378.2008.00592.x.

    Article  PubMed  Google Scholar 

  7. Watabe H, Mitsushima T, Yamaji Y, Okamoto M, Wada R, Kokubo T, et al. Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study. Gut. 2005;54(6):764–8. doi:10.1136/gut.2004.055400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Aikou S, Ohmoto Y, Gunji T, Matsuhashi N, Ohtsu H, Miura H, et al. Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening. Gastroenterology. 2011;141(3):837–45. doi:10.1053/j.gastro.2011.05.040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kaise M, Miwa J, Tashiro J, Ohmoto Y, Morimoto S, Kato M, et al. The combination of serum trefoil factor 3 and pepsinogen testing is a valid non-endoscopic biomarker for predicting the presence of gastric cancer: a new marker for gastric cancer risk. J Gastroenterol. 2011;46(6):736–45. doi:10.1007/s00535-011-0396-8.

    Article  CAS  PubMed  Google Scholar 

  10. Xiao P, Ling H, Lan G, Liu J, Hu H, Yang R. Trefoil factors: gastrointestinal-specific proteins associated with gastric cancer. Clin Chim Acta Int J Clin Chem. 2015;450:127–34. doi:10.1016/j.cca.2015.08.004.

    Article  CAS  Google Scholar 

  11. Hosokawa O. Can a serological test for selecting high-risk groups before endoscopy reduce gastric cancer deaths? Gastric Cancer. 2013;16(3):280–1. doi:10.1007/s10120-012-0199-5.

    Article  PubMed  Google Scholar 

  12. Huang Z, Zhang X, Lu H, Wu L, Wang D, Zhang Q, et al. Serum trefoil factor 3 is a promising non-invasive biomarker for gastric cancer screening: a monocentric cohort study in China. BMC Gastroenterol. 2014;14:74. doi:10.1186/1471-230x-14-74.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Xu CC, Yue L, Wei HJ, Zhao WW, Sui AH, Wang XM, et al. Significance of TFF3 protein and Her-2/neu status in patients with gastric adenocarcinoma. Pathol Res Pract. 2013;209(8):479–85. doi:10.1016/j.prp.2013.04.017.

    Article  CAS  PubMed  Google Scholar 

  14. Perry JK, Kannan N, Grandison PM, Mitchell MD, Lobie PE. Are trefoil factors oncogenic? Trends Endocrinol Metab TEM. 2008;19(2):74–81. doi:10.1016/j.tem.2007.10.003.

    Article  CAS  PubMed  Google Scholar 

  15. Dhar DK, Wang TC, Tabara H, Tonomoto Y, Maruyama R, Tachibana M, et al. Expression of trefoil factor family members correlates with patient prognosis and neoangiogenesis. Clin Cancer Res. 2005;11(18):6472–8. doi:10.1158/1078-0432.ccr-05-0671.

    Article  CAS  PubMed  Google Scholar 

  16. Peterson AJ, Menheniott TR, O’Connor L, Walduck AK, Fox JG, Kawakami K, et al. Helicobacter pylori infection promotes methylation and silencing of trefoil factor 2, leading to gastric tumor development in mice and humans. Gastroenterology. 2010;139(6):2005–17. doi:10.1053/j.gastro.2010.08.043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wong WM, Poulsom R, Wright NA. Trefoil peptides. Gut. 1999;44(6):890–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kjellev S. The trefoil factor family-small peptides with multiple functionalities. Cell Mol Life Sci CMLS. 2009;66(8):1350–69. doi:10.1007/s00018-008-8646-5.

    Article  CAS  PubMed  Google Scholar 

  19. Ribieras S, Tomasetto C, Rio MC. The pS2/TFF1 trefoil factor, from basic research to clinical applications. Biochim Biophys Acta. 1998;1378(1):F61–77.

    CAS  PubMed  Google Scholar 

  20. Plaut AG. Trefoil peptides in the defense of the gastrointestinal tract. N Engl J Med. 1997;336(7):506–7. doi:10.1056/nejm199702133360712.

    Article  CAS  PubMed  Google Scholar 

  21. Kaise M, Miwa J, Fujimoto A, Tashiro J, Tagami D, Sano H, et al. Influence of Helicobacter pylori status and eradication on the serum levels of trefoil factors and pepsinogen test: serum trefoil factor 3 is a stable biomarker. Gastric Cancer. 2013;16(3):329–37. doi:10.1007/s10120-012-0185-y.

    Article  CAS  PubMed  Google Scholar 

  22. Kim HY, Kim N, Kang JM, Park YS, Lee DH, Kim YR, et al. Clinical meaning of pepsinogen test and Helicobacter pylori serology in the health check-up population in Korea. Eur J Gastroenterol Hepatol. 2009;21(6):606–12. doi:10.1097/MEG.0b013e3283086757.

    Article  PubMed  Google Scholar 

  23. Madsen J, Nielsen O, Tornoe I, Thim L, Holmskov U. Tissue localization of human trefoil factors 1, 2, and 3. J Histochem Cytochem. 2007;55(5):505–13. doi:10.1369/jhc.6A7100.2007.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank the Institute for Cancer Research, Keimyung University Dongsan Medical Center, for advising and helping experimental process. The biospecimens for this study were provided by the Keimyung Human Bio-Resource Bank (KHBB), a member of the National Biobank of Korea, which is supported by the Ministry of Health and Welfare.

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Correspondence to Kyung Sik Park.

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Lee, J.Y., Park, K.S., Lee, HG. et al. Comparison of serum trefoil factor 3 with the pepsinogen test for the screening of diffuse-type gastric cancer. Clin Exp Med 17, 403–410 (2017). https://doi.org/10.1007/s10238-016-0426-1

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  • DOI: https://doi.org/10.1007/s10238-016-0426-1

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