Research Papers:

Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis

Kei Mitsuhashi _, Katsuhiko Nosho, Yasutaka Sukawa, Yasutaka Matsunaga, Miki Ito, Hiroyoshi Kurihara, Shinichi Kanno, Hisayoshi Igarashi, Takafumi Naito, Yasushi Adachi, Mami Tachibana, Tokuma Tanuma, Hiroyuki Maguchi, Toshiya Shinohara, Tadashi Hasegawa, Masafumi Imamura, Yasutoshi Kimura, Koichi Hirata, Reo Maruyama, Hiromu Suzuki, Kohzoh Imai, Hiroyuki Yamamoto and Yasuhisa Shinomura

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Oncotarget. 2015; 6:7209-7220. https://doi.org/10.18632/oncotarget.3109

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Kei Mitsuhashi1, Katsuhiko Nosho1, Yasutaka Sukawa2, Yasutaka Matsunaga1, Miki Ito1, Hiroyoshi Kurihara1, Shinichi Kanno1, Hisayoshi Igarashi1, Takafumi Naito1, Yasushi Adachi1, Mami Tachibana1, Tokuma Tanuma1,3, Hiroyuki Maguchi3, Toshiya Shinohara4, Tadashi Hasegawa5, Masafumi Imamura6, Yasutoshi Kimura6, Koichi Hirata6, Reo Maruyama7, Hiromu Suzuki7, Kohzoh Imai8, Hiroyuki Yamamoto9,*, Yasuhisa Shinomura9,*

1Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan

2Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

3Department of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan

4Department of Pathology, Teine Keijinkai Hospital, Sapporo, Japan

5Department of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan

6Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan

7Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan

8The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

9Department 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: [email protected]

Keywords: Fusobacterium, microbiota, pancreas, miR-31, survival

Received: December 04, 2014     Accepted: January 08, 2015     Published: March 13, 2015


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.

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