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Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis
Open accessAbstract
OBJECTIVE: Accumulating evidence links the intestinal microbiota and colorectal carcinogenesis. Fusobacterium nucleatum may promote colorectal tumour growth and inhibit T cell-mediated immune responses against colorectal tumours. Thus, we hypothesised that the amount of F. nucleatum in colorectal carcinoma might be associated with worse clinical outcome. DESIGN: We used molecular pathological epidemiology database of 1069 rectal and colon cancer cases in the Nurses' Health Study and the Health Professionals Follow-up Study, and measured F. nucleatum DNA in carcinoma tissue. Cox proportional hazards model was used to compute hazard ratio (HR), controlling for potential confounders, including microsatellite instability (MSI, mismatch repair deficiency), CpG island methylator phenotype (CIMP), KRAS, BRAF, and PIK3CA mutations, and LINE-1 hypomethylation (low-level methylation). RESULTS: Compared with F. nucleatum-negative cases, multivariable HRs (95% CI) for colorectal cancer-specific mortality in F. nucleatum-low cases and F. nucleatum-high cases were 1.25 (0.82 to 1.92) and 1.58 (1.04 to 2.39), respectively, (p for trend=0.020). The amount of F. nucleatum was associated with MSI-high (multivariable odd ratio (OR), 5.22; 95% CI 2.86 to 9.55) independent of CIMP and BRAF mutation status, whereas CIMP and BRAF mutation were associated with F. nucleatum only in univariate analyses (p<0.001) but not in multivariate analysis that adjusted for MSI status. CONCLUSIONS: The amount of F. nucleatum DNA in colorectal cancer tissue is associated with shorter survival, and may potentially serve as a prognostic biomarker. Our data may have implications in developing cancer prevention and treatment strategies through targeting GI microflora by diet, probiotics and antibiotics.
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“Numerous studies, of multiple cohorts, of patients with CRC worldwide have found similar associations.23–27”
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Metadata
- Authors
- Mima, K., Nishihara, R., Qian, Z. R., Cao, Y., Sukawa, Y., Nowak, J. A., Yang, J., Dou, R., Masugi, Y., Song, M., Kostic, A. D., Giannakis, M., Bullman, S., Milner, D. A., Baba, H., Giovannucci, E. L., Garraway, L. A., Freeman, G. J., Dranoff, G., Garrett, W. S., Huttenhower, C., Meyerson, M., Meyerhardt, J. A., Chan, A. T., Fuchs, C. S., & Ogino, S.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Kumamoto University (JP)
- Corresponding author
- Ogino, Shuji
- ORCID
- Mima, Kosuke
- Nishihara, Reiko
- Qian, Zhi Rong
- Cao, Yin
- Sukawa, Yasutaka
- Nowak, Jonathan A
- Yang, Juhong
- Dou, Ruoxu
- Masugi, Yohei
- Song, Mingyang
- Kostic, Aleksandar D
- Giannakis, Marios
- Bullman, Susan
- Milner, Danny A
- Baba, Hideo
- Giovannucci, Edward L
- Garraway, Levi A
- Freeman, Gordon J
- Dranoff, Glenn
- Garrett, Wendy S
- Huttenhower, Curtis
- Meyerson, Matthew
- Meyerhardt, Jeffrey A
- Chan, Andrew T
- Fuchs, Charles S
- Ogino, Shuji
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2015-08-26
- Volume
- 65
- Issue
- 12
- Pages
- 1973-1980
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC4769120
- OpenAlex
- W2199896469
- Cited by
- 1,080
- References
- 53
- Citations by year
- 2026: 108 · 2025: 116 · 2024: 131 · 2023: 119 · 2022: 141 · 2021: 140 · 2020: 105 · 2019: 71 · 2018: 64 · 2017: 47 · 2016: 34 · 2015: 4
- FWCI
- 21.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (KL2TR001100)
- National Cancer Institute (P50CA127003, R01CA151993, R01CA118553, R01CA137178, R35CA197735, P01CA087969, R01CA169141, K07CA122826, P01CA055075, UM1CA186107, UM1CA167552, K07CA190673, R01CA154426)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK098311)
- National Center for Advancing Translational Sciences
- 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 › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- Fusobacterium nucleatum, colorectal cancer, rectal cancer, colon cancer, prognosis, colorectal cancer-specific mortality, tumor microbiome, microsatellite instability, CpG island methylator phenotype, BRAF mutation, prognostic factors, gut microbiota, antitumor immunity
- MeSH terms
- Aged, Carcinoma, Female, Follow-Up Studies, Humans, Male, Middle Aged, Mutation, Neoplasm Staging, Phenotype, Prognosis, Prospective Studies, Research Design, Biomarkers, Tumor, Colorectal Neoplasms, Databases, Factual, Proto-Oncogene Proteins p21(ras), Fusobacterium nucleatum, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins B-raf, Kaplan-Meier Estimate, Microsatellite Instability, Class I Phosphatidylinositol 3-Kinases
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