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Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome

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Abstract

Commensal bacteria in the colon may play a role in colorectal cancer (CRC) development. Recent studies from North America showed that Fusobacterium nucleatum (Fn) infection is over-represented in disease tissue versus matched normal tissue in CRC patients. Using quantitative real-time polymerase chain reaction (qPCR) of DNA extracted from colorectal tissue biopsies and surgical resections of three European cohorts totalling 122 CRC patients, we found an over-abundance of Fn in cancerous compared to matched normal tissue (p < 0.0001). To determine whether Fn infection is an early event in CRC development, we assayed Fn in colorectal adenoma (CRA) tissue from 52 Irish patients. While for all CRAs the Fn level was not statistically significantly higher in disease versus normal tissue (p = 0.06), it was significantly higher for high-grade dysplasia (p = 0.015). As a secondary objective, we determined that CRC patients with low Fn levels had a significantly longer overall survival time than patients with moderate and high levels of the bacterium (p = 0.008). The investigation of Fn as a potential non-invasive biomarker for CRC screening showed that, while Fn was more abundant in stool samples from CRC patients compared to adenomas or controls, the levels in stool did not correlate with cancer or adenoma tissue levels from the same individuals. This is the first study examining Fn in the colonic tissue and stool of European CRC and CRA patients, and suggests Fn as a novel risk factor for disease progression from adenoma to cancer, possibly affecting patient survival outcomes. Our results highlight the potential of Fn detection as a diagnostic and prognostic determinant in CRC patients.

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Acknowledgements

Funding for the study was provided by the Health Research Board of Ireland (project grant nos. HRA_PHS/2011/3 to DJH and TRA/2007/26 to JHMP). The Czech component was supported by IGA grant nos. NT12025-4 and NT14329-3. We wish to thank Dr. Robert Holt and Dr. Mauro Castellarin (BC Cancer Research Centre, Vancouver, BC, V5Z 1 L3, Canada) for providing us with an aliquot of gDNA from the cultured Fn strain CC53 as a positive control for the qPCR assays and advice on the assay.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Centre for Systems Medicine and Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, York House, York Street, Dublin 2, Ireland

    L. Flanagan, J. Schmid, J. H. M. Prehn & D. J. Hughes

  2. Department of Medicine II, Universitätsmedizin Mannheim, Ruprecht-Karls-Universität Heidelberg, Mannheim, Germany

    M. Ebert

  3. Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic

    P. Soucek

  4. Biomedical Centre, Medical School Pilsen, Charles University in Prague, Pilsen, Czech Republic

    P. Soucek, T. Kunicka, V. Liska & J. Bruha

  5. 3rd Faculty of Medicine, Charles University, Prague, Czech Republic

    T. Kunicka

  6. Department of Surgery, Teaching Hospital and Medical School Pilsen, Charles University in Prague, Pilsen, Czech Republic

    V. Liska & J. Bruha

  7. Department of Colorectal Surgery, Adelaide and Meath Hospital, Dublin 24, Ireland

    P. Neary & N. Dezeeuw

  8. Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France

    M. Tommasino

  9. Nutritional Epidemiology Group, International Agency for Research on Cancer, Lyon, France

    M. Jenab

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  1. L. Flanagan
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Flanagan, L., Schmid, J., Ebert, M. et al. Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J Clin Microbiol Infect Dis 33, 1381–1390 (2014). https://doi.org/10.1007/s10096-014-2081-3

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