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 Jun;46(6):736-45. doi: 10.1007/s00535-011-0396-8. Epub 2011 Apr 1.


Background: A valid biomarker for predicting the presence of gastric cancer may contribute to reducing deaths from this disease. Although pepsinogen (PG) testing has been introduced as a predictor, its predictive power is not satisfactory. We examined whether serum trefoil factor (TFF) could be a non-endoscopic predictor of the presence of gastric cancer.

Methods: Gastric cancer patients who underwent preoperative endoscopy were sequentially recruited. Individuals who underwent a thorough medical checkup were enrolled as non-cancer controls. Serum levels of TFF1, TFF2, TFF3, Helicobacter pylori antibody, PG I, and PG II were examined.

Results: We studied 192 gastric cancer patients aged 64.3 ± 9.7 years and 1254 non-cancer controls aged 52.3 ± 12.4 years. In the age/gender-matched analysis (187 cases and 561 controls), significant relationships were demonstrated between gastric cancer presence and TFF3 (P < 0.0001), the PGI/II ratio (P < 0.0001), H. pylori antibody (P = 0.001), TFF1 (P = 0.012), and TFF2 (P = 0.020). The area under the receiver-operating characteristic curve for predicting gastric cancer presence was comparably high for all factors (0.893) and for the combination of TFF3 and the PG test (0.883), but was significantly (P < 0.0001) lower for the PG test alone (0.823). A positive PG test showed a sensitivity of 67% and specificity of 82%, whereas a combination of TFF3 and PG testing showed a sensitivity of 80% and specificity of 80% in predicting the presence of gastric cancer.

Conclusion: The combination of serum TFF3 and PG testing might be a valid non-endoscopic biomarker for predicting the presence of gastric cancer.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pepsinogen A / blood*
  • Peptides / blood*
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Sensitivity and Specificity
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / pathology
  • Trefoil Factor-2
  • Trefoil Factor-3


  • Biomarkers, Tumor
  • Peptides
  • TFF2 protein, human
  • TFF3 protein, human
  • Trefoil Factor-2
  • Trefoil Factor-3
  • Pepsinogen A