Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome
Open accessAbstract
Commensal bacteria in the colon may play a role in colorectal cancer (CRC) development. Recent studies from North America showed that Fusobacterium nucleatum (Fn) infection is over-represented in disease tissue versus matched normal tissue in CRC patients. Using quantitative real-time polymerase chain reaction (qPCR) of DNA extracted from colorectal tissue biopsies and surgical resections of three European cohorts totalling 122 CRC patients, we found an over-abundance of Fn in cancerous compared to matched normal tissue (p < 0.0001). To determine whether Fn infection is an early event in CRC development, we assayed Fn in colorectal adenoma (CRA) tissue from 52 Irish patients. While for all CRAs the Fn level was not statistically significantly higher in disease versus normal tissue (p = 0.06), it was significantly higher for high-grade dysplasia (p = 0.015). As a secondary objective, we determined that CRC patients with low Fn levels had a significantly longer overall survival time than patients with moderate and high levels of the bacterium (p = 0.008). The investigation of Fn as a potential non-invasive biomarker for CRC screening showed that, while Fn was more abundant in stool samples from CRC patients compared to adenomas or controls, the levels in stool did not correlate with cancer or adenoma tissue levels from the same individuals. This is the first study examining Fn in the colonic tissue and stool of European CRC and CRA patients, and suggests Fn as a novel risk factor for disease progression from adenoma to cancer, possibly affecting patient survival outcomes. Our results highlight the potential of Fn detection as a diagnostic and prognostic determinant in CRC patients.
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Numerous studies of multiple cohorts worldwide have found similar associations between Fusobacterium nucleatum and colorectal cancer.
“Numerous studies, of multiple cohorts, of patients with CRC worldwide have found similar associations.23–27”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [23]
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- Authors
- Flanagan, L., Schmid, J., Ebert, M., Soucek, P., Kunicka, T., Liska, V., Bruha, J., Neary, P., Dezeeuw, N., Tommasino, M., Jenab, M., Prehn, J. H. M., & Hughes, D. J.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- Heidelberg University (DE)
- Tallaght University Hospital (IE)
- Centre international de recherche sur le cancer (FR)
- Corresponding author
- Hughes, D. J.
- Venue
- European Journal of Clinical Microbiology & Infectious Diseases
- Published
- 2014-03-06
- Volume
- 33
- Issue
- 8
- Pages
- 1381-1390
- ISSN
- 0934-9723 (ISSN-L)
- 1435-4373
- OpenAlex
- W2095269215
- Cited by
- 498
- References
- 41
- Citations by year
- 2026: 18 · 2025: 41 · 2024: 59 · 2023: 55 · 2022: 49 · 2021: 61 · 2020: 50 · 2019: 57 · 2018: 41 · 2017: 31 · 2016: 19 · 2015: 12 · 2014: 5
- FWCI
- 9.15
- Type
- journal article
- Language
- en
- Open access
- green
- epubs.rcsi.ie
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Clinical Microbiology & Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by-nc-sa)
- 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 › Oncology › Colorectal Cancer Screening and Detection
- Keywords
- Fusobacterium nucleatum, colorectal cancer, colorectal adenoma, colorectal neoplasia, high-grade dysplasia, commensal bacteria, disease progression, overall survival, prognostic factors, cancer screening biomarkers, colonic tissue
- MeSH terms
- Adenoma, Aged, Aged, 80 and over, Feces, Female, Humans, Male, Middle Aged, Neoplasm Staging, Prognosis, Proto-Oncogene Proteins, Colorectal Neoplasms, Cohort Studies, Tumor Suppressor Protein p53, Proto-Oncogene Proteins p21(ras), Fusobacterium nucleatum, Disease Progression, ras Proteins, Mutation, Missense, Proto-Oncogene Proteins B-raf, Kaplan-Meier Estimate, Bacterial Load, Molecular Typing
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