title: Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.
abstract: Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Kei
authors: K
authors: Mitsuhashi
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Katsuhiko
authors: K
authors: Nosho
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
authors: Yasutaka
authors: Y
authors: Sukawa
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Yasutaka
authors: Y
authors: Matsunaga
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Miki
authors: M
authors: Ito
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Hiroyoshi
authors: H
authors: Kurihara
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Shinichi
authors: S
authors: Kanno
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Hisayoshi
authors: H
authors: Igarashi
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Takafumi
authors: T
authors: Naito
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Yasushi
authors: Y
authors: Adachi
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Mami
authors: M
authors: Tachibana
authors: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
authors: Tokuma
authors: T
authors: Tanuma
authors: Department of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
authors: Hiroyuki
authors: H
authors: Maguchi
authors: Department of Pathology, Teine Keijinkai Hospital, Sapporo, Japan.
authors: Toshiya
authors: T
authors: Shinohara
authors: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Tadashi
authors: T
authors: Hasegawa
authors: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Masafumi
authors: M
authors: Imamura
authors: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Yasutoshi
authors: Y
authors: Kimura
authors: Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Koichi
authors: K
authors: Hirata
authors: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Reo
authors: R
authors: Maruyama
authors: Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Hiromu
authors: H
authors: Suzuki
authors: The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Kohzoh
authors: K
authors: Imai
authors: Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan.
authors: Hiroyuki
authors: H
authors: Yamamoto
authors: Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan.
authors: Yasuhisa
authors: Y
authors: Shinomura
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005673:Fusobacterium / Q000472:pathogenicity*; D005674:Fusobacterium Infections / Q000150:complications*; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000150:complications / Q000235:genetics / Q000382:microbiology*; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: Fusobacterium; miR-31; microbiota; pancreas; survival