Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway: F. Nucleatum and molecular features of serrated lesions
Open accessAbstract
Human gut microbiota is being increasingly recognized as a player in colorectal cancers (CRCs). Evidence suggests that Fusobacterium nucleatum (F. nucleatum) may contribute to disease progression and is associated with CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in CRCs; however, to date, there are no reports about the relationship between F. nucleatum and molecular features in the early stage of colorectal tumorigenesis. Therefore, we investigated the presence of F. nucleatum in premalignant colorectal lesions. In total, 465 premalignant lesions (343 serrated lesions and 122 non-serrated adenomas) and 511 CRCs were studied. We determined the presence of F. nucleatum and analyzed its association with molecular features including CIMP, MSI and microRNA-31 status. F. nucleatum was detected in 24% of hyperplastic polyps, 35% of sessile serrated adenomas (SSAs), 30% of traditional serrated adenomas (TSAs) and 33% of non-serrated adenomas. F. nucleatum was more frequently detected in CIMP-high premalignant lesions than in CIMP-low/zero lesions (p = 0.0023). In SSAs, F. nucleatum positivity increased gradually from sigmoid colon to cecum (p = 0.042). F. nucleatum positivity was significantly higher in CRCs (56%) than in premalignant lesions of any histological type (p < 0.0001). In conclusion, F. nucleatum was identified in premalignant colorectal lesions regardless of histopathology but was more frequently associated with CIMP-high lesions. Moreover, F. nucleatum positivity increased according to histological grade, suggesting that it may contribute to the progression of colorectal neoplasia. Our data also indicate that F. nucleatum positivity in SSAs may support the "colorectal continuum" concept.
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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 [24]
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- Authors
- Ito, M., Kanno, S., Nosho, K., Sukawa, Y., Mitsuhashi, K., Kurihara, H., Igarashi, H., Takahashi, T., Tachibana, M., Takahashi, H., Yoshii, S., Takenouchi, T., Hasegawa, T., Okita, K., Hirata, K., Maruyama, R., Suzuki, H., Imai, K., Yamamoto, H., & Shinomura, Y.
- Affiliations
- Sapporo Medical University (JP)
- Harvard University (US)
- Keiyukai Sapporo Hospital (JP)
- NTT (Japan) (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- St. Marianna University School of Medicine (JP)
- Corresponding author
- Nosho, Katsuhiko
- ORCID
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2015-03-13
- Volume
- 137
- Issue
- 6
- Pages
- 1258-1268
- ISSN
- 0020-7136 (ISSN-L)
- OpenAlex
- W1896348045
- Cited by
- 288
- References
- 53
- Citations by year
- 2026: 20 · 2025: 13 · 2024: 23 · 2023: 29 · 2022: 34 · 2021: 37 · 2020: 29 · 2019: 32 · 2018: 31 · 2017: 23 · 2016: 15 · 2015: 2
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Daiwa Securities Health Foundation
- Ono Cancer Research Foundation
- Takeda Science Foundation
- the Japan Society for the Promotion of Science (JSPS) Challenging Exploratory Research (25670371)
- The Suhara Memorial Foundation
- Yuasa Memorial Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Keywords
- Fusobacterium nucleatum, colorectal cancer, premalignant colorectal lesions, sessile serrated adenoma, traditional serrated adenoma, hyperplastic polyps, CpG island methylator phenotype, microsatellite instability, miR-31, gut microbiota, histological grade
- MeSH terms
- Aged, Cecum, Colon, Female, Fusobacterium Infections, Humans, Male, Colorectal Neoplasms, Fusobacterium nucleatum, CpG Islands, DNA Methylation, MicroRNAs, Microsatellite Instability, Carcinogenesis
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