Abstract 5957: Molecular characteristics of gut microbiota in patients with gastric cancer: The DELIVER trial (JACCRO GC-08)

Abstract Microbiome analysis has attracted attention in recent years as a tool to monitor individual health status. In particular, gut microbiota is closely related to autoimmunity, and detailed study of gut microbiota may enable prediction of the health status of individuals.Here, we aimed to conduct a detailed study to identify gastric cancer-specific gut microbiota and compare the data between patients with gastric cancer and healthy individuals. Toward this, we extracted DNA from feces of patients with advanced gastric cancer enrolled in the observational/translational study, the DELIVER trial (JACCRO GC-08: UMIN000030850) which evaluated clinical outcomes of nivolumab and developed host-related biomarkers for nivolumab in 500 patients with advanced gastric cancer, and obtained their sequence data at an average of 5 Gbps using whole-genome shotgun sequencing. We then performed genus classification and functional pathway analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG).We analyzed differences in bacterial composition using the data of 476 Japanese patients with advanced gastric cancer (median age 70y, median BMI 20.0, 71% male, 37.0% of patients with relapse, 55.5% with previous gastrectomy) and public database of 106 healthy cases. Bifidobacterium, Anaerostipes, and Parabacteroides were predominant in the healthy individuals, whereas Streptococcus, Lactobacillus, and Odoribacter were predominant in patients with advanced gastric cancer. Furthermore, the KEGG pathway analysis showed that butanoate and pyruvate metabolism were enriched in the healthy individuals, whereas factors such as ABC transporters and ribosomes were enriched in the patients with advanced gastric cancer. Clustering analysis broadly classified the patients with advanced gastric cancer and healthy individuals into two clusters, and the clustering using pathway data enabled clearer classification of the patients with advanced gastric cancer and healthy individuals than the clustering using flora analysis. Additionally, the healthy individuals had higher bacterial flora diversity compared to the patients with advanced gastric cancer.We thus successfully identified the molecular characteristic of microbial genera and functional pathways in the gut in patients with advanced gastric cancer. We conclude that fecal metagenomic shotgun sequencing analysis might be used to detect gastric cancer. Citation Format: Ryo Matoba, Hiroshi Iijima, Yasuhiro Sakamoto, Ryohei Kawabata, Atsushi Ishiguro, Yusuke Akamaru, Yosuke Kito, Hiroshi Yabusaki, Jin Matsuyama, Masazumi Takahashi, Akitaka Makiyama, Takahisa Suzuki, Masahiro Tsuda, Hisateru Yasui, Jun Hihara, Toru Masuzawa, Hiroyuki Okuda, Junji Kawada, Shuhei Suzuki, Hisato Kawakami, Takako Eguchi Nakajima, Kei Muro, Wataru Ichikawa, Masashi Fujii, Yu Sunakawa. Molecular characteristics of gut microbiota in patients with gastric cancer: The DELIVER trial (JACCRO GC-08) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5957.