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Association of<i>Fusobacterium</i>species in pancreatic cancer tissues with molecular features and prognosis

Oncotarget · 2015 · Vol. 6(9) · pp. 7209–7220
Kei MitsuhashiKatsuhiko NoshoYasutaka SukawaYasutaka MatsunagaMiki ItoHiroyoshi KuriharaShinichi KannoHisayoshi IgarashiTakafumi NaitoYasushi AdachiMami TachibanaTokuma TanumaHiroyuki MaguchiToshiya ShinoharaTadashi HasegawaMasafumi ImamuraYasutoshi KimuraKoichi HirataReo MaruyamaHiromu SuzukiKohzoh ImaiHiroyuki YamamotoYasuhisa Shinomura

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.

Pancreatic and Hepatic Oncology ResearchGut microbiota and healthSalivary Gland Tumors Diagnosis and TreatmentMedicineInternal medicineFusobacteriumMedical schoolHepatologyClinical OncologyFamily medicineCancerGeneral surgeryMedical education

MeSH terms

AgedFemaleFusobacteriumFusobacterium InfectionsHumansMaleMiddle AgedPancreatic NeoplasmsPhenotypePrognosisRegression AnalysisBiomarkers, TumorMultivariate AnalysisProportional Hazards ModelsTreatment Outcome

Funding

  • Pancreas Research Foundation of Japan
  • Daiwa Securities Health Foundation
  • Suhara Memorial Foundation
  • Japan Society for the Promotion of Science
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