SFRP2 and RPRM as methylation based serum biomarkers for the detection of gastric cancer.

BACKGROUND: Gastric cancer (GC) has a high mortality rate due to the diagnosis in advanced stages. Aberrant DNA methylation is the earliest event in carcinogenesis and can be noninvasively detected in cell-free DNA (cfDNA) from gastric cancer patients. METHODS: A total of 143 serum samples were analyzed, including 33 GC patients, 30 chronic gastritis (ChG) patients, and 80 healthy individuals. Additionally, tissue samples were collected from 30 GC patients (stages I-IV) and 38 ChG patients. Methylation patterns of ten genes were examined in GC cells, as well as in serum and tissue samples from GC, ChG, and control groups using methylation-specific qPCR. Statistical evaluations were conducted on various parameters including Ct differences, categorical variables, sensitivity, and specificity. RESULTS: APC, CDH1, RASSF1A, hMLH1, RUNX3, p16, SFRP2, RNF180, PCDH10, and RPRM were all significantly hypermethylated in the tissues of GC patients compared to those with ChG (P < 0.001). SFRP2, RPRM, APC, PCDH10, and RNF180 genes were analyzed in sera of 3 groups. Among them, SFRP2 methylation was detected in 71.87% of GC, 16.6% of ChG and 8.8% of the control group. The methylation frequencies of RPRM were 66.6% in GC, 13.3% in ChG, and 7.5% in the control group. In a dual-gene panel assay combining SFRP2 and RPRM, the sensitivity and specificity for detecting gastric cancer in serum samples were 57.58% and 96.25%, respectively, when comparing the cancer and control groups. The sensitivity was 78.79%, the specificity was 90.00% and AUC was 0.931 for GC and control groups (P < 0.0001). The sensitivity was 78.79%, the specificity was 83.33% and AUC was 0.879 for the discrimination of GC and ChG (P < 0.0001). CONCLUSIONS: Methylation of 10 genes were studied and a prototype early diagnosis tool for GC utilizing SFRP2 and RPRM with high sensitivity and specificity was developed.