Combined Detection of Plasma ZIC1, HOXD10 and RUNX3 Methylation is a Promising Strategy for Early Detection of Gastric Cancer and Precancerous Lesions

We try to explore the value of aberrant DNA methylation of several cancer-related genes in plasma as non-invasive biomarkers for gastric cancer (GC) and precancerous lesions. By using methylation-specific polymerase chain reaction assay we determined the methylation status of three selected genes ZIC1, HOXD10 and RUNX3 in blood samples from patients with GC and precancerous lesions. We discovered that the methylation rate of ZIC1, HOXD10 and RUNX3 increased significantly in the progression of gastric carcinogenesis. Methylation of ZIC1 was associated with positive serum CA19-9, while that of HOXD10 was related to H. pylori status, serum CA19-9 and CEA levels and tumor invasion depth. The Odds ratios (ORs) of ZIC1, HOXD10 and RUNX3 methylation for predicting GC were 4.285 (95% CI: 2.435-7.542), 3.133 (95% CI: 1.700-5.775) and 2.674 (95% CI: 1.441-4.960), while for predicting "gastric cancer and intraepithelial neoplasia" (GnI), the ORs were 12.011 (95% CI: 0.050-28.564), 9.174 (95% CI: 3.220-26.135) and 12.794 (95% CI: 4.115-39.778), respectively. In terms of combined detection of these three genes, the sensitivity was 91.6% for GC and 89.8% for GnI, with the highest Youden index in both GC and GnI determination. Conclusively, combined detection of ZIC1, HOXD10 and RUNX3 promoter hypermethylation might be a promising strategy for early detection of GC and precancerous lesions.