// Kei Mitsuhashi 1 , Katsuhiko Nosho 1 , Yasutaka Sukawa 2 , Yasutaka Matsunaga 1 , Miki Ito 1 , Hiroyoshi Kurihara 1 , Shinichi Kanno 1 , Hisayoshi Igarashi 1 , Takafumi Naito 1 , Yasushi Adachi 1 , Mami Tachibana 1 , Tokuma Tanuma 1, 3 , Hiroyuki Maguchi 3 , Toshiya Shinohara 4 , Tadashi Hasegawa 5 , Masafumi Imamura 6 , Yasutoshi Kimura 6 , Koichi Hirata 6 , Reo Maruyama 7 , Hiromu Suzuki 7 , Kohzoh Imai 8 , Hiroyuki Yamamoto 9, * , Yasuhisa Shinomura 9, * 1 Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan 2 Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 3 Department of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan 4 Department of Pathology, Teine Keijinkai Hospital, Sapporo, Japan 5 Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan 6 Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan 7 Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan 8 The Institute of Medical Science, The University of Tokyo, Tokyo, Japan 9 Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan * These authors have contributed equally to this work Correspondence to: Katsuhiko Nosho, e-mail: nosho@sapmed.ac.jp Keywords: Fusobacterium, microbiota, pancreas, miR-31, survival Received: December 04, 2014&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: January 08, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: March 13, 2015 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.

Association ofFusobacteriumspecies in pancreatic cancer tissues with molecular features and prognosis