Pan-cancer analysis reveals tumor microbiome associations with host molecular aberrations

Abstract Host-microbiome interaction is known to play a pivotal role in the cancer ecosystem, yet the associations have not been systematically investigated at the pan-cancer and the multi-omics level. Here, we evaluated nearly 10,000 samples across 32 cancer types collected from The Cancer Genome Atlas (TCGA), to investigate the association between the tumor microbiome (taxa, n=1,630) and tumor microenvironment composition (cell types, n=20), epigenome (CpG island methylation, n=30,716), transcriptome (gene expression, n=10,216) and proteome (protein expression, n=193). We identified 836,738 candidate associations between the tumor microbiome and host molecular aberrations across multiple cancers. Besides cancer-specific associations, we also revealed recurrent pan-cancer associations between microbes ( Lachnoclostridium , Flammeovirga , Terrabacter and Campylobacter ) and immune cells, as well as between microbes ( Collimonas and Sutterella ) and fibroblasts, which were further validated by cell type estimations derived from pathological images and methylation data. We also identified several potential microbe and gene/protein expression associations mediated by DNA methylation using the sequential mediation analysis. Furthermore, our survival analysis demonstrated that tumor microbes may affect the patient’s overall survival and progression-free survival. Finally, a user-friendly web portal, Multi-Omics and Microbiome Associations in Cancer (MOMAC) was constructed for users to explore potential host-microbe interactions in cancer. Graphical abstract