Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway

Miki Ito, Shinichi Kanno, Katsuhiko Nosho, Yasutaka Sukawa, Kei Mitsuhashi, Hiroyoshi Kurihara, Hisayoshi Igarashi, Taiga Takahashi, Mami Tachibana, Hiroaki Takahashi, Shinji Yoshii, Toshinao Takenouchi, Tadashi Hasegawa, Kenji Okita, Koichi Hirata, Reo Maruyama, Hiromu Suzuki, Kohzoh Imai, Hiroyuki Yamamoto, Yasuhisa Shinomura

Research output: Contribution to journalArticle

96 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1258-1268
Number of pages11
JournalInternational Journal of Cancer
Volume137
Issue number6
DOIs
Publication statusPublished - 2015 Sep 1
Externally publishedYes

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Keywords

  • BRAF
  • colon polyp
  • colorectum
  • dysplasia
  • Fusobacterium
  • KRAS
  • microbiome
  • miR-31
  • MLH1
  • serrated neoplasia pathway

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. (2015). Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway. International Journal of Cancer, 137(6), 1258-1268. https://doi.org/10.1002/ijc.29488