Circulating methylated Septin 9 and ring finger protein 180 for noninvasive diagnosis of early gastric cancer

BACKGROUND: Gastric cancer (GC) has a poor prognosis due to patients often being diagnosed at an advanced stage, when metastasis has already occurred. To improve the 5-year survival rate and reduce the number of cancer-related deaths in patients with GC, noninvasive methods for early detection need to be developed. This study aimed to evaluate the value of circulating methylated Septin 9 (SEPT9) and ring finger protein 180 (RNF180) for the early diagnosis of GC. METHODS: Seventy-four patients with early GC, 99 patients with benign gastric diseases (BGD) (inflammation, polyps, intestinal metaplasia, ulcers, and erosion), and 57 cases with no evidence of disease (NED) were enrolled. Methylated SEPT9 and RNF180 in circulating cell-free DNA in blood samples from each group were detected, and the positivity rates were calculated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), confidence interval (CI), and area under the curve (AUC) were determined for methylated SEPT9 and RNF180 in relation to early GC. RESULTS: As a diagnostic target, methylated SEPT9 had a sensitivity of 28.3% (95% CI: 18.5–40.0%), specificity of 94.2% (95% CI: 89.3–97.3%), and AUC value of 0.616 (95% CI: 52.0–71.1%). Methylated RNF180 had a sensitivity of 32.4% (95% CI: 22.0–44.3%), specificity of 89.7% (95% CI: 83.9–94.0%), and AUC value of 0.636 (95% CI: 54.2–73.0%). A combination of the two yielded a sensitivity of 40.5% (95% CI: 29.3–52.6%), specificity of 85.3% (95% CI: 78.7–90.4%), and AUC value of 0.65 (95% CI: 55.7–74.4%). CONCLUSIONS: Methylated SEPT9 and RNF180 could be used as diagnostic biomarkers for early gastric cancer (EGC).