Min-Jeong Kim, Han-Na Kim, Jonathan P Jacobs, Hyo-Joon Yang
{"title":"Combined DNA Methylation and Gastric Microbiome Marker Predicts <i>Helicobacter pylori</i>-Negative Gastric Cancer.","authors":"Min-Jeong Kim, Han-Na Kim, Jonathan P Jacobs, Hyo-Joon Yang","doi":"10.5009/gnl230348","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aims: </strong>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 <i>Helicobacter pylori</i>-negative GC.</p><p><strong>Methods: </strong>In this case-control study, we conducted quantitative methylation-specific polymerase chain reaction to measure the methylation levels of <i>DKK3</i>, <i>SFRP1</i>, <i>EMX1</i>, <i>NKX6-1</i>, <i>MIR124-3</i>, and <i>TWIST1</i> in the gastric mucosa from 75 <i>H. pylori</i>-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.</p><p><strong>Results: </strong>The methylation levels of <i>DKK3</i>, <i>SFRP1</i>, <i>EMX1</i>, <i>MIR124-3</i>, and <i>TWIST1</i> 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 <i>TWIST1</i> was an independent predictor for <i>H. pylori</i>-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 <i>H. pylori</i>-negative GC after adjusting for age, sex, and atrophy (OR, 50.00; 95% CI, 1.69 to 1,476; p=0.024).</p><p><strong>Conclusions: </strong>The combination of TWIST1 methylation and GC microbiome index may offer potential as a biomarker for predicting <i>H. pylori</i>-negative GC.</p>","PeriodicalId":12885,"journal":{"name":"Gut and Liver","volume":" ","pages":"611-620"},"PeriodicalIF":3.4000,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249944/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gut and Liver","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.5009/gnl230348","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/21 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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 Helicobacter pylori-negative GC.
Methods: In this case-control study, we conducted quantitative methylation-specific polymerase chain reaction to measure the methylation levels of DKK3, SFRP1, EMX1, NKX6-1, MIR124-3, and TWIST1 in the gastric mucosa from 75 H. pylori-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 DKK3, SFRP1, EMX1, MIR124-3, and TWIST1 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 TWIST1 was an independent predictor for H. pylori-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 H. pylori-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 H. pylori-negative GC.
期刊介绍:
Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut and Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology.
Gut and Liver is jointly owned and operated by 8 affiliated societies in the field of gastroenterology, namely: the Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, the Korean College of Helicobacter and Upper Gastrointestinal Research, the Korean Association for the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, the Korean Pancreatobiliary Association, and the Korean Society of Gastrointestinal Cancer.