Value of Methylation Status of RPRM, SDC2, and TCF4 Genes in Plasma for Gastric Adenocarcinoma Screening

OBJECTIVE: To explore the clinical value of the combined screening of the methylation statuses of the RPRM, SDC2, and TCF4 genes in plasma of gastric cancer patients. METHODS: Differential expressed genes (DEGs) were selected from the Gene Expression Omnibus database, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using DAVID, and a protein-protein interaction network was constructed. Hub genes were obtained using Cytoscape. Screening results combined with literature reports identified three genes (RPRM, SDC2, and TCF4). Further analysis was done using biopsies collected through gastroscopy at Shanxi Cancer Hospital from January 8, 2020 to February 22, 2021. The patients were divided into two groups: gastric adenocarcinoma group, and control group which are not gastric adenocarcinoma according to pathological or gastroscopic results. The methylation statuses of the three genes in peripheral blood plasma were detected by fluorescence polymerase chain reaction, and the relationships between the positive rates of the three combined genes with pathology and/or gastroscopy results were analyzed. The clinical value of the combined detection of the three genes was evaluated according to these indicators. The diagnostic specificity and sensitivity of this detective method were analyzed. RESULTS: A total of 197 DEGs were identified and 12 hub genes were obtained. The enriched functions and pathways of DEGs include regulation of cell proliferation, extracellular space, cytokine activity, and pathways in cancer. The combination of RPRM, SDC2, and TCF4 gene methylation had a specificity of 93.39% and sensitivity of 80.33%. The combined positive rate of RPRM, SDC2, and TCF4 gene methylation in patients with gastric adenocarcinoma was significantly higher compared with those without gastric adenocarcinoma (χ(2)=151.179, P<0.05). CONCLUSION: Combined detection of RPRM, SDC2, and TCF4 gene methylation in peripheral blood plasma maybe helpful in screening for gastric adenocarcinoma, and maybe a complementary method to gastroscopy and serum tumor markers.