Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis
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Abstract Background: Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis. Methods: We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer–specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer–specific mortality, and somatic mutations. Results: F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer–specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07–3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer–specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations. Conclusions: F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer–specific mortality and specific somatic mutated genes. Impact: Our findings identify the F. nucleatum subspecies animalis as negatively impacting colorectal cancer mortality, which may occur through a stage shift and its effect on chemoresistance.
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CRC has often been associated with Fusobacterium species and clades, as have several other bacterial species.
“It is worth noting that CRC has often been associated with Fusobac terium species and clades, as have several other bacterial spe cies, 31,47,48”
From Global genetic diversity of human gut microbiome species is related to geographic location and host health (2025) · cites this paper as [48]
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A distinct Fusobacterium nucleatum clade dominates the colorectal cancer niche
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- Authors
- Borozan, I., Zaidi, S. H., Harrison, T. A., Phipps, A. I., Zheng, J., Lee, S., Trinh, Q. M., Steinfelder, R. S., Adams, J., Banbury, B. L., Berndt, S. I., Brezina, S., Buchanan, D. D., Bullman, S., Cao, Y., Farris, A. B., Figueiredo, J. C., Giannakis, M., Heisler, L. E., Hopper, J. L., Lin, Y., Luo, X., Nishihara, R., Mardis, E. R., Papadopoulos, N., Qu, C., Reid, E. E. G., Thibodeau, S. N., Harlid, S., Um, C. Y., Hsu, L., Gsur, A., Campbell, P. T., Gallinger, S., Newcomb, P. A., Ogino, S., Sun, W., Hudson, T. J., Ferretti, V., & Peters, U.
- Affiliations
- Ontario Institute for Cancer Research (CA)
- Fred Hutch Cancer Center (US)
- National Institutes of Health (US)
- Medical University of Vienna (AT)
- The Royal Melbourne Hospital (AU)
- Washington University in St. Louis (US)
- Emory University (US)
- Cedars-Sinai Medical Center (US)
- Broad Institute (US)
- The University of Melbourne (AU)
- Brigham and Women's Hospital (US)
- Nationwide Children's Hospital (US)
- Johns Hopkins University (US)
- Mayo Clinic (US)
- Umeå University (SE)
- American Cancer Society (US)
- University of Washington (US)
- 1Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
- Harvard University (US)
- Corresponding author
- Ferretti, Vincent
- Peters, Ulrike
- ORCID
- Borozan, Ivan
- Zaidi, Syed H.
- Harrison, Tabitha A.
- Phipps, Amanda I.
- Zheng, Jiayin
- Lee, Stephen
- Trinh, Quang M.
- Steinfelder, Robert S.
- Adams, Jeremy
- Banbury, Barbara L.
- Berndt, Sonja I.
- Brezina, Stefanie
- Buchanan, Daniel D.
- Bullman, Susan
- Cao, Yin
- Farris, Alton B.
- Figueiredo, Jane C.
- Giannakis, Marios
- Heisler, Lawrence E.
- Hopper, John L.
- Lin, Yi
- Luo, Xuemei
- Nishihara, Reiko
- Mardis, Elaine R.
- Papadopoulos, Nickolas
- Qu, Conghui
- Thibodeau, Stephen N.
- Harlid, Sophia
- Um, Caroline Y.
- Hsu, Li
- Gsur, Andrea
- Campbell, Peter T.
- Newcomb, Polly A.
- Ogino, Shuji
- Sun, Wei
- Hudson, Thomas J.
- Ferretti, Vincent
- Peters, Ulrike
- Venue
- Cancer Epidemiology, Biomarkers & Prevention
- Published
- 2022-01-01
- Volume
- 31
- Issue
- 1
- Pages
- 210-220
- ISSN
- 1055-9965 (ISSN-L)
- 1538-7755
- PMC
- PMC8755593
- OpenAlex
- W3210643297
- Cited by
- 57
- References
- 48
- Citations by year
- 2026: 9 · 2025: 23 · 2024: 10 · 2023: 10 · 2022: 5
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Epidemiology Biomarkers & Prevention (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NCI NIH (U01 CA137088, U01 CA164930, R01 CA176272)
- NCI (U01 CA167551, U01 CA074794, U24 CA074794, R01 CA076366)
- OFCCR (U01 CA074783, U24 CA074783)
- Austrian Research Funding Agency (829675)
- 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 › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- Fusobacterium nucleatum, colorectal cancer, colorectal cancer-specific mortality, tumor microbiome, NusA, NusG, microsatellite instability, POLE mutation, TP53 mutation, chemoresistance, tumor stage, right-sided tumors, advanced cancer, somatic mutations
- MeSH terms
- Humans, RNA, Ribosomal, 16S, Colorectal Neoplasms, Fusobacterium nucleatum, Carcinogenesis
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