Association of Fusobacterium Species in Pancreatic Cancer Tissues With Molecular Features and Prognosis

Oncotarget. 2015 Mar 30;6(9):7209-20. doi: 10.18632/oncotarget.3109.

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.

Keywords: Fusobacterium; miR-31; microbiota; pancreas; survival.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism
  • CpG Islands
  • DNA Methylation
  • Epigenesis, Genetic
  • Female
  • Fusobacterium / pathogenicity*
  • Fusobacterium Infections / complications*
  • Gene Expression Profiling
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Multivariate Analysis
  • Pancreatic Neoplasms / complications
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / microbiology*
  • Phenotype
  • Prognosis
  • Proportional Hazards Models
  • Regression Analysis
  • Sequence Analysis, DNA
  • Treatment Outcome

Substances

  • Biomarkers, Tumor