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

AbstractHost-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 patients 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 O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/536730v2_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@70f74eorg.highwire.dtl.DTLVardef@7c3078org.highwire.dtl.DTLVardef@152354dorg.highwire.dtl.DTLVardef@299282_HPS_FORMAT_FIGEXP M_FIG C_FIG