FOLH1 as a novel biomarker for risk stratification in gastric intestinal metaplasia

BACKGROUND Gastric intestinal metaplasia (GIM) is a precancerous condition associated with gastric cancer (GC). However, biomarkers that predict progression from GIM to GC remain unclear. AIM To investigate the potential of FOLH1 as a novel tissue-based biomarker for identifying patients with GIM at high risk of progression to GC. METHODS This single-center retrospective cohort study was conducted at Wangjing Hospital and included 68 patients diagnosed with GIM. GIM samples were obtained sequentially from the antrum using endoscopic biopsies. Patients were assigned to the progressive group (P) if they developed high-grade intraepithelial neoplasia, intramucosal carcinoma, or adenocarcinoma during the 5-year follow-up; patients whose GIM remained stable were assigned to the non-progression group (N). A subset of 8 patients (4 from group P and 4 from group N) was used to identify potential biomarkers using differentially expressed genes and weighted gene correlation network analysis based on digital spatial profiling. The remaining 60 patients were used to validate candidate biomarkers using histologic evaluation, immunohistochemical staining, and immunofluorescent staining. RESULTS In the 8-patient discovery cohort, FOLH1 expression was significantly decreased in the epithelium of patients in group P compared with those in group N. In the 60-patient validation cohort, FOLH1 was a reliable biomarker for predicting malignant transformation from GIM to GC, with a sensitivity of 0.967 and a specificity of 1.000. Using Youden’s index, the optimal diagnostic cutoff value for FOLH1 was 0.302, corresponding to an integral optical density of 31.46. CONCLUSION FOLH1 may serve as a tissue-based biomarker for predicting progression from GIM to GC.