Screening Biomarker as an Alternative to Endoscopy for the Detection of Early Gastric Cancer: The Combination of Serum Trefoil Factor Family 3 and Pepsinogen
Hyun Seok Lee, Seong Woo Jeon, Sachiyo Nomura, Yasuyuki Seto, Yong Hwan Kwon, Su Youn Nam, Yuko Ishibashi, Hiroshi Ohtsu, Yasukazu Ohmoto, Hae Min Yang, Hyun Seok Lee, Seong Woo Jeon, Sachiyo Nomura, Yasuyuki Seto, Yong Hwan Kwon, Su Youn Nam, Yuko Ishibashi, Hiroshi Ohtsu, Yasukazu Ohmoto, Hae Min Yang
Abstract
Objective: The serum pepsinogen test has limitation in its predictive power as a noninvasive biomarker for gastric cancer screening. We aimed to investigate whether the combination of TFF3 and pepsinogen could be an effective biomarker for the detection of gastric cancer even in the early stages.
Methods: In total, 281 patients with early gastric cancer (EGC), who underwent endoscopic submucosal dissection in Korea, and 708 healthy individuals from Japan were enrolled in the derivation cohort. The validation cohort included 30 Korean patients with EGC and 30 Korean healthy control blood donors. Serum TFF3 levels were examined using enzyme-linked immunosorbent assay.
Results: Using a cutoff of 6.73 ng/mL in the derivation cohort, the sensitivity of the combination of tests for EGC detection was superior (87.5%) to that of TFF3 (80.4%) or pepsinogen test alone (39.5%). Similarly, in the validation cohort, the sensitivity of TFF3 plus pepsinogen was higher (90.4%) than that of TFF3 (80.0%) or pepsinogen test alone (33.3%).
Conclusion: The combination of serum TFF3 and pepsinogen is a more effective noninvasive biomarker for gastric cancer detection compared with pepsinogen or TFF3 alone, even in EGC. This trial is registered with NCT03046745.
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References
- Ferlay J., Soerjomataram I., Dikshit R., et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer. 2015;136(5):E359–E386. doi: 10.1002/ijc.29210.
- Park H. A., Nam S. Y., Lee S. K., et al. The Korean guideline for gastric cancer screening. Journal of the Korean Medical Association. 2015;58(5):p. 373. doi: 10.5124/jkma.2015.58.5.373.
- Hamashima C., Shibuya D., Yamazaki H., et al. The Japanese guidelines for gastric cancer screening. Japanese Journal of Clinical Oncology. 2008;38(4):259–267. doi: 10.1093/jjco/hyn017.
- Miki K., Ichinose M., Kakei N., et al. The clinical application of the serum pepsinogen I and II levels as a mass screening method for gastric cancer. Advances in Experimental Medicine and Biology. 1995;362:139–143.
- Yoon H., Kim N. Diagnosis and management of high risk group for gastric cancer. Gut and Liver. 2015;9(1):5–17. doi: 10.5009/gnl14118.
- Plaut A. G. Trefoil peptides in the defense of the gastrointestinal tract. The New England Journal of Medicine. 1997;336(7):506–507. doi: 10.1056/NEJM199702133360712.
- Kjellev S. The trefoil factor family – small peptides with multiple functionalities. Cellular and Molecular Life Sciences. 2009;66(8):1350–1369. doi: 10.1007/s00018-008-8646-5.
- Wong W. M., Poulsom R., Wright N. A. Trefoil peptides. Gut. 1999;44(6):890–895. doi: 10.1136/gut.44.6.890.
- Xiao P., Ling H., Lan G., Liu J., Hu H., Yang R. Trefoil factors: gastrointestinal-specific proteins associated with gastric cancer. Clinica Chimica Acta. 2015;450:127–134. doi: 10.1016/j.cca.2015.08.004.
- Hosokawa O. Can a serological test for selecting high-risk groups before endoscopy reduce gastric cancer deaths? Gastric Cancer. 2013;16(3):280–281. doi: 10.1007/s10120-012-0199-5.
- Aikou S., Ohmoto Y., Gunji T., et al. Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening. Gastroenterology. 2011;141(3):837–845.e7. doi: 10.1053/j.gastro.2011.05.040.
- 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. Journal of Medical Screening. 2004;11(3):141–147. doi: 10.1258/0969141041732184.
- Huang Z., Zhang X., Lu H., et al. Serum trefoil factor 3 is a promising non-invasive biomarker for gastric cancer screening: a monocentric cohort study in China. BMC Gastroenterology. 2014;14(1):p. 74. doi: 10.1186/1471-230X-14-74.
- Kim H. Y., Kim N., Kang J. M., et al. Clinical meaning of pepsinogen test and Helicobacter pylori serology in the health check-up population in Korea. European Journal of Gastroenterology & Hepatology. 2009;21(6):606–612. doi: 10.1097/MEG.0b013e3283086757.
- Kaise M., Miwa J., Fujimoto A., 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):329–337. doi: 10.1007/s10120-012-0185-y.
- Madsen J., Nielsen O., Tornøe I., Thim L., Holmskov U. Tissue localization of human trefoil factors 1, 2, and 3. Journal of Histochemistry & Cytochemistry. 2007;55(5):505–513. doi: 10.1369/jhc.6A7100.2007.
- Lee J. Y., Park K. S., Lee H.-G., et al. Comparison of serum trefoil factor 3 with the pepsinogen test for the screening of diffuse-type gastric cancer. Clinical and Experimental Medicine. 2017;17(3):403–410. doi: 10.1007/s10238-016-0426-1.
- Perry J. K., Kannan N., Grandison P. M., Mitchell M. D., Lobie P. E. Are trefoil factors oncogenic? Trends in Endocrinology & Metabolism. 2008;19(2):74–81. doi: 10.1016/j.tem.2007.10.003.
- Dhar D. K., Wang T. C., Tabara H., et al. Expression of trefoil factor family members correlates with patient prognosis and neoangiogenesis. Clinical Cancer Research. 2005;11(18):6472–6478. doi: 10.1158/1078-0432.CCR-05-0671.
- Peterson A. J., Menheniott T. R., O'Connor L., 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):2005–2017. doi: 10.1053/j.gastro.2010.08.043.
- Kaise M., Miwa J., Tashiro J., 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. Journal of Gastroenterology. 2011;46(6):736–745. doi: 10.1007/s00535-011-0396-8.
Source: PubMed