Trefoil Factors as Screening Biomarkers for Gastric Cancer and Premalignant Lesions: A Cross-Sectional Population-Based Cohort Study

Background: The lack of effective biomarkers for screening gastric cancer (GC) and premalignant lesions (PMLs) is a significant roadblock in the prevention and early intervention of GC. We aimed to identify noninvasive biomarkers to improve the screening of high-risk populations. Methods: We evaluated 25,000 adults residing in Wuwei. We collected baseline characteristics, GC risk indicators, including trefoil factors (TFF1–3), endoscopy diagnosis, and pathological information. We analyzed the data to determine the association of risk biomarkers with the progression of GC and the prediction capacities of these biomarkers using odds ratio (OR)-adjusted models and receiver operating characteristic (ROC) curve analyses. Results: TFF1 and TFF2 serum levels showed incremental changes from the PMLs to the GC group, with the highest serum TFF3 levels reported in the intestinal metaplasia group. TFF1 and TFF2 had significant predictive values in the PMLs and GC in the three OR-adjusted models but not in the non-atrophic gastritis group. Similar results were obtained after adjusting for all biomarkers and risk factors wherein the ORs (95 % confidence intervals) of TFF1 and TFF2 in the GC group were 2.71 (1.57–4.67) and 2.87 (1.75–4.71), respectively ( P  < 0.001). The combination of TFF1–3 showed the largest area under the curve across all four groups (chronic atrophic gastritis [0.74], intestinal metaplasia [0.79], low-grade intraepithelial neoplasia/dysplasia [0.79], and GC [0.84]), making it the best-fit ROC. Conclusions: TFF1, TFF2, and the combination of TFF1–3 can serve as sensitive, specific, and noninvasive biomarkers for detecting GC and PMLs, facilitating the early identification of these lesions.