Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma

Castellarin, Mauro; Warren, René L.; Freeman, J. Douglas; Dreolini, Lisa; Krzywinski, Martin; Strauss, Jaclyn; Barnes, Rebecca; Watson, Peter; Allen-Vercoe, Emma; Moore, Richard A.; Holt, Robert A.

doi:10.1101/gr.126516.111

Cited by 2,043Gut microbiota and healthOral microbiology and periodontitis researchClostridium difficile and Clostridium perfringens research

Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma

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Castellarin, Mauro, Warren, René L., Freeman, J. Douglas, Dreolini, Lisa, Krzywinski, Martin, Strauss, Jaclyn, Barnes, Rebecca, Watson, Peter +3 more·2012·Genome Research

DOI 10.1101/gr.126516.111PMC PMC3266037

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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.

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F. nucleatum has been proved to be associated with CRC development and progression.
“which has been proved to be associated with CRC development and progression45,46.”
From A tumor microenvironment-specific gene expression signature predicts chemotherapy resistance in colorectal cancer patients (2021) · cites this paper as [45]
The opening summary reports F. nucleatum overabundance in colorectal tumors and a positive association with lymph node metastasis. But the Results (page not provided) say its involvement in tumorigenesis remains undetermined and that further study is needed to assess early-stage progression. The source therefore supports an association with CRC and a marker of progression, not a proven role in its development or progression. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Intratumor bacteria have been reported in many tumor types.
“Intratumor bacteria have been reported in many tumor types (2-19)”
From The human tumor microbiome is composed of tumor type–specific intracellular bacteria (2020) · cites this paper as [11]
Fusobacterium DNA and RNA sequences are increased in tumor compared with non-tumor specimens.
“Two independent studies reported increased levels of Fusobacterium DNA and RNA sequences in tumor compared with non-tumor specimens.21, 22”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [21]
A high abundance of F. nucleatum is associated with regional lymph node metastasis and shorter survival.
“A high abundance of F.nucleatum is also associated with regional lymph node metastasis and shorter survival [9, 10].”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [10]

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Authors: Castellarin, M., Warren, R. L., Freeman, J. D., Dreolini, L., Krzywinski, M., Strauss, J., Barnes, R., Watson, P., Allen-Vercoe, E., Moore, R. A., & Holt, R. A.
Affiliations: BC Cancer Agency (CA)
University of Guelph (CA)
ORCID: Castellarin, Mauro
Krzywinski, Martin
Barnes, Rebecca
Watson, Peter
Holt, Robert A.
Venue: Genome Research
Publisher: Cold Spring Harbor Laboratory
Published: 2011-10-18
Volume: 22
Issue: 2
Pages: 299-306
ISSN: 1088-9051 (ISSN-L)
DOI: 10.1101/gr.126516.111
PMC: PMC3266037
OpenAlex: W2140679462
Cited by: 2,043
References: 42
Citations by year: 2026: 119 · 2025: 153 · 2024: 192 · 2023: 188 · 2022: 183 · 2021: 230 · 2020: 191 · 2019: 162 · 2018: 143 · 2017: 109 · 2016: 101 · 2015: 81 · 2014: 69 · 2013: 76 · 2012: 40
Type: posted content
Language: en
Open access: hybrid
doi.org
Licence: other-oa
Locations: Genome Research (publishedVersion, other-oa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: Genome British Columbia
Canadian Institutes of Health Research
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
Keywords: Fusobacterium nucleatum, colorectal cancer, gut microbiota, RNA-seq, lymph node metastasis, tumor microbiome
MeSH terms: Fusobacterium Infections, Humans, Intestine, Large, Phylogeny, Colorectal Neoplasms, Cluster Analysis, Genome, Bacterial, Fusobacterium nucleatum, Cell Line, Tumor, Metagenome

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Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma

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