Fusobacterium nucleatum Enrichment in Colorectal Tumor Tissue: Associations With Tumor Characteristics and Survival Outcomes

Abstract

Background and Aims: Fusobacterium nucleatum (Fn) is linked to colorectal cancer (CRC) etiology and survival. We hypothesized that CRC tumor attributes and survival are associated with the amount and presence of Fn in tumors. Methods: Fn abundance was measured via droplet digital polymerase chain reaction in patient-matched CRC tumor and normal tissue samples from 859 Puget Sound CRC Cohort participants. Fn enrichment was defined as the continuous difference in normalized abundance between patient-matched tumor and normal tissue samples. Fn presence in tumor was classified categorically as not present, low, or high, regardless of Fn status in matched normal tissue. Associations of Fn enrichment and presence with tumor site, stage, DNA mismatch repair (MMR) status, CpG island methylator phenotype (CIMP) status, BRAF and KRAS mutation status, and molecular subtypes based on combinations of tumor markers were assessed using logistic regression. Associations of Fn enrichment and presence with CRC survival was estimate with Cox regression. Results: Fn was present in 20% of tumor tissues and 10% of normal tissues, with higher average abundance in tumors. High Fn presence was independently associated with deficient MMR (dMMR) status and in the context of molecular subtypes for type 1 tumors (dMMR, CIMP-high, BRAF-mutated) and type 5 tumors (dMMR, CIMP-low or negative, BRAF-wildtype). Fn enrichment was associated with type 5 and type 2 tumors (proficient MMR, CIMP-high, BRAF-mutated). Fn enrichment and presence were associated with poorer CRC survival, with some suggestion that associations differed by MMR status. Conclusion: Detectable Fn in CRC tissue is associated with certain CRC tumor attributes and survival; however, associations may vary based on Fn definition.

Keywords

• Fusobacterium
• Intratumoral Microbiome
• Tumor Microenvironment
• CRC
• PSCCC