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.