LAUSR

Objective: The microbiome is associated with the pathogenesis and progression of disease in gastric cancer (GC). Eradication of Helicobacter pylori has reduced overall GC incidence, however, gastroesophageal cancer (GEJC) continues to increase. While there are oncologic differences between GEJC and GC, distinctions based on microbial profiles are unknown. In this study, we characterize differences in the microbial profiles of GEJC and GC. Methods: 562 patients with microsatellite stable GC (n=303) and GEJC (n=259) who had an institutional Integrated Mutation Profiling of Actionable Cancer Targets assay on the primary tumor were included in the study. A validated microbiome bioinformatics pipeline that is generalizable across multiple next generation sequencing platforms was utilized to compare microbial enrichment and alpha diversity between GC and GEJC, defined by type 1-3 Siewert classification. Results: Over 20 unique microbial species were enriched in GC when compared to GEJC, including Helicobacter and Lymphocryptovirus (Table 1). Prevotella had increased incidence in GEJC (OR:1.57,95%CI:1.02,2.41). Siewert type 2 and 3 GEJC had a significantly lower alpha diversity compared to GC. There was no significant difference in alpha diversity between GC and Siewert type 1 GEJC. Conclusion: There are distinct differences in microbial enrichment and alpha diversity between GEJC and GC. Helicobacter and Lymphocryptovirus, the genus family for Epstein Bar Virus, were noted to have the highest odds ratios in the GC group. Our findings showing the reduced incidence of microbes in GEJC which are the current targets of GC screening, prevention, and therapy, have implications in evaluating optimal preventative and treatment strategies in GEJC. Table 1. Microbes with enrichment in gastric cancer (GC) when compared to gastroesophageal cancer (GEJC) Microbes OR (95% Confidence Interval) p-value Helicobacter 85.40 (5.191, 1404.81) 0.002 Lymphocryptovirus 6.83 (2.3120,.17) 0.001 Pelagibacterium 6.01 (1.71, 21.06) 0.005 Gluconacetobacter 5.14 (1.70, 15.53) 0.004 Myxococcus 5.14 (1.70, 15.53) 0.004 Kribbella 4.48 (1.46, 13.74) 0.009 Celeribacter 3.46 (1.43, 8.37) 0.006 Halomonas 3.46 (1.43, 8.37) 0.006 Nakamurella 3.35 (1.46, 7.71) 0.004 Nitrobacter 2.91 (1.40, 6.05) 0.004 Pseudogulbenkiania 2.80 (1.30, 6.03) 0.009 Mycobacteroides 2.78 (1.33, 5.81) 0.006 Polaromonas 2.70 (1.49, 4.90) 0.001 Meiothermus 2.54 (1.41, 4.57) 0.002 Sphingopyxis 2.44 (1.33, 4.46) 0.004 Mesorhizobium 2.38 (1.32, 4.30) 0.004 Staphylococcus 2.23 (1.37, 3.62) 0.001 Thermus 2.13 (1.22, 3.70) 0.008 Mycolicibacterium 1.99 (1.29, 3.07) 0.002 Mycobacterium 1.95 (1.23, 3.08) 0.005 Lactobacillus 1.94 (1.17, 3.22) 0.01 Citation Format: Miseker Abate, Harrison Drebin, Shoji Shimada, Santosh Vardhana, Smita Sihag, Vivian E. Strong, Chad Vanderbilt. Distinct differences in microbial enrichment and diversity identified between gastric and gastroesophageal junction adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5890.