Abstract LB155: Increase in Pseudomonas and Shigella is associated to disease severity and Veillonella parvula is linked to promoter DNA methylation levels in endoscopic gastric biopsies

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Abstract Introduction: Clinically useful molecular tools to triage gastric cancer patients in low resource settings are not currently available. We previously found that promoter methylation of IRF4, ELMO1, CLIP4 and MSC and a Global DNA Methylation Index > 4 in endoscopic biopsies, can be used as a molecular tool in gastric cancer risk stratification algorithms. We hypothesized that the microbiota provides a broad spectrum of taxa identification, a distinct sequence read record, and robust detection sensitivity, which can be used in gastric cancer risk stratification algorithms. Methods: We performed 16sRNA metagenomic sequencing to study the association between the gastric epithelium microbiome and DNA methylation alterations previously associated to gastric cancer risk in endoscopic tissue samples from a subset of cancer (n=14) and gastritis (n=10) participants from a prospective, observational study (n= 576) in high-risk gastric cancer clinics in Lima, Peru. The inclusion criterion were gastro-duodenal symptoms (ICD9-CM code 535) for gastritis controls and a clinical diagnosis of gastric cancer (ICD9-CM code 151) for cases, all determined by pathologists in Peru. A pathologist at Johns Hopkins School of Medicine reviewed a random sample of slides. Informed written consent was obtained from all patients included in the study. The Institutional Review Board of Johns Hopkins School of Medicine (NA_00020633) approved the research protocols. Results: Beta diversity comparisons using non-metric multidimensional scaling (NMDS), discriminated cancer from gastritis samples. We identified a predominance of Helicobacter pylori (p=0.001), Pseudomonas(p=0.002) and Shigella (p=0.005) in cancer samples. We also found and inverse association between Veillonella parvula (p=0.03) and DNA methylation of IRF4, ELMO1, CLIP4 and MSC in cancer samples. Conclusion: Preliminary results warrant further exploration of DNA methylation and microbiome linkages in the transition from a normal to a premalignant gastric phenotype, which can be used to develop affordable PCR based, point-of-care assays, for high-risk gastric cancer clinics worldwide. Citation Format: Laura Palmieri, Kelvin Navarro, Robert Gilman, Martha Jahuira Arias, Anne Jedlicka, Amanda Dziedzic, Ashley Ramos-Lopez, Amanda Garcia Negron, Juan Combe, Gloria Vargas, William Prado, James White, Mariana Brait, David Sidransky, Filipa Godoy Vitorino, Rafael E. Guerrero-Preston. Increase in Pseudomonas and Shigella is associated to disease severity and Veillonella parvula is linked to promoter DNA methylation levels in endoscopic gastric biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB155.

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