title: Human Microbiome Fusobacterium Nucleatum in Esophageal Cancer Tissue Is Associated with Prognosis.
abstract: OBJECTIVE
  Fusobacterium nucleatum (F. nucleatum) is a component of the human microbiome that primarily inhabits the oral cavity. It causes periodontal disease and has also been implicated in the development of human cancers. Although there are several reports of the relationship between F. nucleatum and the clinical outcome in human cancers, its prognostic significance in esophageal cancer remains unclear.
  
  
  METHODS
  We quantified F. nucleatum DNA in 325 resected esophageal cancer specimens by qPCR. Significant pathways in F. nucleatum-positive esophageal cancer tissues were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using microarray data.
  
  
  RESULTS
  Esophageal cancer tissues contained significantly more F. nucleatum DNA than matched normal esophageal mucosa (P = 0.021; n = 60). F. nucleatum DNA was detected in 74 of 325 cases (23%). F. nucleatum DNA positivity was significantly associated with tumor stage, but not with sex, age, performance status, tobacco use, alcohol use, histology, tumor location, or preoperative treatment. F. nucleatum DNA positivity was also significantly associated with cancer-specific survival [log-rank P = 0.0039; univariate HR = 2.01; 95% confidence interval (CI), 1.22-3.23; P = 0.0068; multivariate HR = 1.78; 95% CI, 1.06-2.94; P = 0.031]. The top-ranked KEGG pathway in F. nucleatum-positive tissues was "cytokine-cytokine receptor interaction." A significant relationship between F. nucleatum and the chemokine CCL20 was validated by IHC.
  
  
  CONCLUSIONS
  F. nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. F. nucleatum might also contribute to aggressive tumor behavior through activation of chemokines, such as CCL20. Clin Cancer Res; 22(22); 5574-81. ©2016 AACR.
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Kensuke
authors: K
authors: Yamamura
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Yoshifumi
authors: Y
authors: Baba
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Shigeki
authors: S
authors: Nakagawa
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Kosuke
authors: K
authors: Mima
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Keisuke
authors: K
authors: Miyake
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Kenichi
authors: K
authors: Nakamura
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Hiroshi
authors: H
authors: Sawayama
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Koichi
authors: K
authors: Kinoshita
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Takatsugu
authors: T
authors: Ishimoto
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Masaaki
authors: M
authors: Iwatsuki
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Yasuo
authors: Y
authors: Sakamoto
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Yoichi
authors: Y
authors: Yamashita
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Naoya
authors: N
authors: Yoshida
authors: Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Masayuki
authors: M
authors: Watanabe
authors: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. hdobaba@kumamoto-u.ac.jp.
authors: Hideo
authors: H
authors: Baba
mesh_terms: D000368:Aged; D018925:Chemokines / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D005260:Female; D016967:Fusobacterium nucleatum / Q000235:genetics*; D006801:Humans; D008297:Male; D064307:Microbiota / Q000235:genetics*; D011379:Prognosis
chemical_list: D018925:Chemokines; D004269:DNA, Bacterial