Combined DNA Methylation and Gastric Microbiome Marker Predicts -Negative Gastric Cancer

Background/aims: While DNA methylation and gastric microbiome are each associated with gastric cancer (GC), their combined role in predicting GC remains unclear. This study investigated the potential of a combined DNA methylation and gastric microbiome signature to predict -negative GC.

Methods: In this case-control study, we conducted quantitative methylation-specific polymerase chain reaction to measure the methylation levels of , , , , , and in the gastric mucosa from 75 -negative patients, including chronic gastritis (CG), intestinal metaplasia (IM), and GC. A combined analysis of DNA methylation and gastric microbiome, using 16S rRNA gene sequencing, was performed in 30 of 75 patients.

Results: The methylation levels of , , , , and were significantly higher in patients with GC than in controls (all q<0.05). MIR124-3 and TWIST1 methylation levels were higher in patients with IM than those with CG and also in those with GC than in those with IM (all q<0.05). A higher methylation level of was an independent predictor for -negative GC after adjusting for age, sex, and atrophy (odds ratio [OR], 15.15; 95% confidence interval [CI], 1.58 to 145.46; p=0.018). The combination of TWIST1 methylation and GC microbiome index (a microbiome marker) was significantly associated with -negative GC after adjusting for age, sex, and atrophy (OR, 50.00; 95% CI, 1.69 to 1,476; p=0.024).

Conclusions: The combination of TWIST1 methylation and GC microbiome index may offer potential as a biomarker for predicting -negative GC.