Cited by 288Gut microbiota and healthGenetic factors in colorectal cancerColorectal Cancer Screening and Detection

Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway: F. Nucleatum and molecular features of serrated lesions

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Ito, Miki, Kanno, Shinichi, Nosho, Katsuhiko, Sukawa, Yasutaka, Mitsuhashi, Kei, Kurihara, Hiroyoshi, Igarashi, Hisayoshi, Takahashi, Taiga +12 more·2015·International Journal of Cancer

Abstract

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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  1. Yamauchi M, Lochhead P, Morikawa T, et al. Colorectal cancer: a tale of two sides or a contin- uum? Gut 2012;61:794-7.
  2. Fujita K, Yamamoto H, Matsumoto T, et al. Ses- sile serrated adenoma with early neoplastic pro- gression: a clinicopathologic and molecular study. Am J Surg Pathol 2011;35:295-304.
  3. Mitsuhashi K, Nosho K, Sukawa Y, et al. Associa- tion of Fusobacterium species in pancreatic can- cer tissues with molecular features and prognosis. Oncotarget, in press.
  4. V C 2015 UICC 10970215, 2015, 6, chromatin regulators. Gastroenterology 2014;146: 530-38 e5. · DOI
  5. V C 2015 UICC 10970215, 2015, 6, · DOI

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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
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
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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