Abstract 647: Landscapes of intra-tumoral and intra-cellular microbiome in gastric cancer progression and correlation with oncogenic and immunological features

Abstract

Abstract Background: Recent studies have pointed to the functional importance of the intra-tumoral microbiome. However, there is a lack of such comprehensive study on gastric cancer (GC). Clarifying the contribution of gastric microbiome to the development, phenotypic heterogeneity and evolution of GC would lead to improvements in prevention, diagnosis, and treatment of this lethal disease. Results: This study collected single-cell RNA sequencing (scRNA-Seq) data generated on a total of 202 samples from 74 GC patients including matched adjacent gastric tissue (n=16), primary tumor (n=65), and metastases from 3 different sites (liver n=8, ovary n=7, peritoneal ascites n=38 and implants n=9), as well as blood samples from 59 patients, together with rich clinical and histopathological information. CSI-Microbes pipeline was applied to extract the uniquely mapped reads to microbial genomes and characterized the abundance and composition of intra-tumoral microbiome across different tissues and histology types. Considerable amount of cell-free microbial nucleic acids were detected within samples. At the specie level, H.pylori was detected with a sensitivity of 76% and specificity of 87%. In addition, H.pylori was almost exclusively enriched in the non-neoplastic adjacent tissues (p=0.01) and primary GCs (p=3.13 × 10−4), but not in blood or metastatic tumors, which is consistent with previous reports. Notably, microbiome detected in the non-neoplastic adjacent tissues were nearly exclusively shared with their paired primary GCs, while primary GCs contained about twice more species than the adjacent tissues, indicating an increased diversity in microbiome species in tumor tissues. The microbiome in patients’ blood samples showed a similar diversity but the abundance and composition differed significantly from that observed in their matched primary GCs. Ascites samples showed a much lower microbiome abundance as well as diversity, exhibiting a clearly distinct landscape. Further analysis identified tissue- and site-specific enrichment of microbiome. In addition, correlation analysis with tumor genetic background, histology subtypes, oncogenic features as well as tumor immune phenotypes revealed interesting associations with microbiome profiles, suggesting the potential impact of intra-tumoral microbiome on tumor and immune cell properties in GC. Lastly, the single-cell intracellular microbiome analysis suggested that a subset of microbiomes was significantly enriched in particular immune cell types, suggesting potential impact of the microbe on anti-tumor immune responses. Conclusions: This study systematically characterized the microbial abundance, distribution, and composition in GC across tissues and sites and provided novel insights into their potential roles in the development, progression, and phenotypic heterogeneity of GC. Citation Format: Fuduan Peng, Enyu Dai, Ruiping Wang, Yuanyuan Zhang, Yanshuo Chu, Guangchun Han, Shumei Song, Xiangdong Cheng, Jaffer Ajani, Jiangjiang Qin, Linghua Wang. Landscapes of intra-tumoral and intra-cellular microbiome in gastric cancer progression and correlation with oncogenic and immunological features [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 647.