The epigenetic study of Fgfr2 as a potential biomarker in the differential diagnosis of intestinal metaplasia and gastric cancer

Abstract

\n Background Epigenetic alterations represent the potential role in the pathological process of cancer development. Epigenetic modulators affect some key gene methylation that can be applied as cancer biomarkers. Gastric cancer is faced with some limitations in diagnosis and differential diagnosis with intestinal metaplasia (IM). Intestinal metaplasia (IM) is generally considered a precancerous lesion in the carcinogenesis of gastric cancer cascade that is a major health burden worldwide. The fibroblast growth factor receptor 2 (FGFR2) gene is a receptor tyrosine kinase in which aberrant expression has a direct connection to GC. The purpose of the present study was to evaluate the prognostic relevance of FGFR2 methylation in the whole blood specimens obtained from patients with GC and IM and normal individual controls to examine the possible implication of epigenetic biomarker for differential diagnosis GC from IM.Material and Methods Appropriate epigenetic control regions in FGFR2 CpGs Island were specified by bioinformatic and differentially methylated regions (DMRs) enrichment analysis. The methylation aberration of FGFR2 selected CPG region was determined using MSRE-PCR and Real-time PCR on DNA extracted from blood samples of 125 participants, including 30 IM cases, 60 GC cases, and 35 normal controls individuals. Results A significant FGFR2 hypomethylation has been obtained in IM (p = 0.01) and GC (p < 0.001) versus the normal control samples. ROC statistical analysis revealed sensitivity (96.67 %) and specificity (100 %) for FGFR2 as DNA epigenetic biomarker diagnostic of gastric cancer test with p < 0.001. These results suggest that the change in the methylation of FGFR2 (AUC = 0.97) is a promising epi-biomarker. Conclusions This study is the first study to show that blood-based biomarkers FGFR2 gene may be a powerful epigenetic biomarker for diagnosing GC and IM and providing insights into gastric cancer pathogenesis and diagnosis.