title: Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome.
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.
authors.affiliation: Centre for Systems Medicine and Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, York House, York Street, Dublin 2, Ireland.
authors.forename: L
authors.initials: L
authors.lastname: Flanagan
authors.forename: J
authors.initials: J
authors.lastname: Schmid
authors.forename: M
authors.initials: M
authors.lastname: Ebert
authors.forename: P
authors.initials: P
authors.lastname: Soucek
authors.forename: T
authors.initials: T
authors.lastname: Kunicka
authors.forename: V
authors.initials: V
authors.lastname: Liska
authors.forename: J
authors.initials: J
authors.lastname: Bruha
authors.forename: P
authors.initials: P
authors.lastname: Neary
authors.forename: N
authors.initials: N
authors.lastname: Dezeeuw
authors.forename: M
authors.initials: M
authors.lastname: Tommasino
authors.forename: M
authors.initials: M
authors.lastname: Jenab
authors.forename: J H M
authors.initials: JH
authors.lastname: Prehn
authors.forename: D J
authors.initials: DJ
authors.lastname: Hughes
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D058491:Bacterial Load; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005243:Feces / Q000382:microbiology; D005260:Female; D016967:Fusobacterium nucleatum / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D020125:Mutation, Missense; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins