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Int J Cancer. 2015 Sep 15;137(6):1258-68. doi: 10.1002/ijc.29488. Epub 2015 Mar 13.

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

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Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
Department of Gastroenterology, Keiyukai Sapporo Hospital, Sapporo, Japan.
Department of Gastroenterology, NTT East Sapporo Hospital, Sapporo, Japan.
Department of Pathology, Keiyukai Sapporo Hospital, Sapporo, Japan.
Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan.


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.


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

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