Blood Based Methylated DNA and Tumor-Specific Protein Analysis in Gastric Cancer Diagnostics

Promoter methylation rates of three tumor suppressor genes were detected in the total cirDNA, derived from plasma and cell-surface-bound fractions, of gastric cancer patients (n = 30) and healthy subjects (n = 30) using MS-PCR. The tumor marker protein levels (CEA, CA 72.4, CA 19.9) were assessed in plasma samples by commercial immunoassay kits. Methylated forms of p15, MGMT and hMLH1genes were detected in the total cirDNA with high rates at II, III and IV stages of gastric cancer. Sensitivity of the MS-PCR-based assay for at least one of methylated p15 and hMLH1 genes in gastric cancer was found to be much higher compared with the sensitivity of the immunoassay for elevated levels of CA 72.4 and CA 19.9 proteins (63 and 30%, respectively). No significant correlation was found between epigenetic and protein markers so indicating their independent development in gastric tumor pathogenesis. To conclude, epigenetic alterations of total cirDNA and elevated levels of tumor-associated proteins were found to be independently associated with gastric cancer indicating their usefulness as complementary diagnostic and prognostic markers for gastric cancer.