title: Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway.
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.
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kanno
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nosho
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Sukawa
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Mitsuhashi
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Kurihara
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Igarashi
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Taiga
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: Department of Gastroenterology, Keiyukai Sapporo Hospital, Sapporo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterology, NTT East Sapporo Hospital, Sapporo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yoshii
authors.affiliation: Department of Pathology, Keiyukai Sapporo Hospital, Sapporo, Japan.
authors.forename: Toshinao
authors.initials: T
authors.lastname: Takenouchi
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Okita
authors.affiliation: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Reo
authors.initials: R
authors.lastname: Maruyama
authors.affiliation: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.affiliation: Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
mesh_terms: D000368:Aged; D063646:Carcinogenesis / Q000235:genetics*; D002432:Cecum / Q000382:microbiology / Q000473:pathology; D003106:Colon / Q000382:microbiology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D005674:Fusobacterium Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology*; D016967:Fusobacterium nucleatum / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D053842:Microsatellite Instability
chemical_list: C534612:MIRN31 microRNA, human; D035683:MicroRNAs
keywords: BRAF; Fusobacterium; KRAS; MLH1; colon polyp; colorectum; dysplasia; miR-31; microbiome; serrated neoplasia pathway