Promoter methylation of tumor-related genes as a potential biomarker using blood samples for gastric cancer detection.

Gene promoter methylation has been reported in gastric cancer (GC). However, the potential applications of blood-based gene promoter methylation as a noninvasive biomarker for GC detection remain to be evaluated. Hence, we performed this analysis to determine whether promoter methylation of 11 tumor-related genes could become a promising biomarker in blood samples in GC. We found that the cyclin-dependent kinase inhibitor 2A ( p16 ), E-cadherin ( CDH1 ), runt-related transcription factor 3 ( RUNX3 ), human mutL homolog 1 ( MLH1 ), RAS association domain family protein 1A ( RASSF1A ), cyclin-dependent kinase inhibitor 2B ( p15 ), adenomatous polyposis coli ( APC ), Glutathione S-transferase P1 ( GSTP1 ), TP53 dependent G2 arrest mediator candidate ( Reprimo ), and O6-methylguanine-DNAmethyl-transferase ( MGMT ) promoter methylation was notably higher in blood samples of patients with GC compared with non-tumor controls. While death-associated protein kinase ( DAPK ) promoter methylation was not correlated with GC. Further analyses demonstrated that RUNX3 , RASSF1A and Reprimo promoter methylation had a good diagnostic capacity in blood samples of GC versus non-tumor controls ( RUNX3 : sensitivity = 63.2% and specificity = 97.5%, RASSF1A : sensitivity = 61.5% and specificity = 96.3%, Reprimo : sensitivity = 82.0% and specificity = 89.0%). Our findings indicate that promoter methylation of the RUNX3 , RASSF1A and Reprimo genes could be powerful and potential noninvasive biomarkers for the detection and diagnosis of GC in blood samples in clinical practices, especially Reprimo gene. Further well-designed (multi-center) and prospective clinical studies with large populations are needed to confirm these findings in the future.