Abstract 5909: Characterization of the lung cancer microbiome using whole genome sequencing

Microbiome studies have been rapidly increasing over the last decade, providing valuable insights into the commensal bacterial contribution to human physiology and disease, including human cancer. Many studies have demonstrated the important roles of the microbiome in cancer progression, anti-tumor immunity, resistance to therapies, metastasis formation, and in some rare cases even cancer development through the production of genotoxins. However, relatively few studies have analyzed the lung cancer microbiome, and both its composition and role in cancer progression are largely unknown. To characterize the microbiome of tumor and matched normal lung tissues, we performed whole-genome sequencing (WGS) in 872 never smokers using the Kraken pipeline. At the phylum level, WGS analyses of tumor and normal samples showed predominantly Proteobacteria and Actinobacteria (58% and 32%, respectively). Notably, we found overall similar microbiome composition in tumor and normal lung tissue samples. At the genus level, Cutibacterium, Klebsiella, Pseudomonas, Sphingomonas, Staphylococcus, and Acinetobacter genera were among the most abundant bacteria in tumor and normal tissues, alike, and the genera Prevotella, Corynebacterium, and Streptococcus were more abundant in tumor samples compared to normal lung tissue. Comparison of alpha diversity at the genus level between tumors and normal samples showed no substantial difference. We are currently investigating whether the microbiome composition varies by lung tumor anatomical location, sex, histology, study subjects’ geographical location, and immune microenvironment. We will also investigate whether the tumor microbiome composition varies in relation to important genomic features, like cancer driver genes and mutational signatures. Finally, we have 16s rRNA seq data from 771 tumor and normal lung tissues from never smokers and we will compare bacterial microbiome composition and diversity based on WGS and 16s rRNA seq for the same samples. This study, based on the largest analysis of lung microbiome to date, is poised to provide important insights into the role of commensal microbiota in shaping lung tumor development and progression. Citation Format: John McElderry, Tongwu Zhang, Jianxin Shi, Maria Teresa Landi. Characterization of the lung cancer microbiome using whole genome sequencing [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 5909.