<i>Fusobacterium nucleatum</i> infection is prevalent in human colorectal carcinoma

TLDR

Infectious agents account for over 15 % of global cancer burden, and the invasive anaerobe Fusobacterium nucleatum—rare in fecal microbiota but previously linked to periodontitis and appendicitis—has not yet been associated with cancer. The authors performed RNA‑seq of colorectal carcinoma and matched normal tissues, subtracted host reads, and validated tumor‑specific overrepresentation of Fusobacterium nucleatum by quantitative PCR in 99 subjects, also isolating an invasive strain from a frozen tumor specimen. Quantitative PCR confirmed that Fusobacterium nucleatum is significantly overrepresented in colorectal tumors compared with matched normal tissue (p = 2.5 × 10⁻⁶) and is positively associated with lymph node metastasis.

Abstract

An estimated 15% or more of the cancer burden worldwide is attributable to known infectious agents. We screened colorectal carcinoma and matched normal tissue specimens using RNA-seq followed by host sequence subtraction and found marked over-representation of Fusobacterium nucleatum sequences in tumors relative to control specimens. F. nucleatum is an invasive anaerobe that has been linked previously to periodontitis and appendicitis, but not to cancer. Fusobacteria are rare constituents of the fecal microbiota, but have been cultured previously from biopsies of inflamed gut mucosa. We obtained a Fusobacterium isolate from a frozen tumor specimen; this showed highest sequence similarity to a known gut mucosa isolate and was confirmed to be invasive. We verified overabundance of Fusobacterium sequences in tumor versus matched normal control tissue by quantitative PCR analysis from a total of 99 subjects ( p = 2.5 × 10 −6 ), and we observed a positive association with lymph node metastasis.