Early warning value of serum TFF3 combined with pepsinogen ratio for monitoring the progression of gastric precancerous lesions: a retrospective study.

OBJECTIVE

Gastric cancer (GC) has high mortality due to late diagnosis. Identifying which patients with gastric low-grade intraepithelial neoplasia (LGIN) will progress to high-grade intraepithelial neoplasia (HGIN) or early gastric cancer (EGC) remains challenging. This study aimed to develop a non-invasive method combining serum TFF3 (reflecting malignant transformation) and pepsinogen ratio (PGR, indicating gastric atrophy) to predict progression.

METHODS

A retrospective multicenter study included patients with confirmed LGIN, available serum, and full follow-up. Progression to HGIN/EGC within 24 months was the primary outcome. TFF3 and PGR were measured using ELISA and chemiluminescence immunoassay, respectively. Propensity score matching (1:4) balanced baseline variables. Predictive performance was assessed via ROC analysis, logistic regression, and Cox models.

RESULTS

After matching, 85 patients (17 progressors) were analyzed. Progressors had higher TFF3 (11.28 vs. 7.15 ng/mL) and lower PGR (2.78 vs. 3.62; both p < 0.001). The combined model showed superior accuracy (AUC = 0.823) versus TFF3 or PGR alone, with sensitivity of 88.2%, specificity of 89.7%, and NPV of 98.3. Progressors exhibited yearly TFF3 increase (+ 1.82 ng/mL) and PGR decrease (-0.41). TFF3 correlated with Ki-67 (ρ = 0.437, p < 0.001).

CONCLUSION

The TFF3 and PGR combination is a non-invasive tool for stratifying LGIN progression risk. Its high NPV safely excludes short-term progression, enabling extended follow-up for low-risk patients and better allocation of endoscopic resources. This approach supports personalized monitoring and may help reduce gastric cancer mortality.