Dataset Information

Fusobacterium nucleatum and Clinicopathologic Features of Colorectal Cancer: Results From the ColoCare Study.

ABSTRACT:

Background

Fusobacterium nucleatum (Fn), a bacterium associated with a wide spectrum of infections, has emerged as a key microbe in colorectal carcinogenesis. However, the underlying mechanisms and clinical relevance of Fn in colorectal cancer (CRC) remain incompletely understood.

Patients and methods

We examined associations between Fn abundance and clinicopathologic characteristics among 105 treatment-naïve CRC patients enrolled in the international, prospective ColoCare Study. Electronic medical charts, including pathological reports, were reviewed to document clinicopathologic features. Quantitative real-time polymerase chain reaction (PCR) was used to amplify/detect Fn DNA in preoperative fecal samples. Multinomial logistic regression was used to analyze associations between Fn abundance and patient sex, age, tumor stage, grade, site, microsatellite instability, body mass index (BMI), alcohol consumption, and smoking history. Cox proportional hazards models were used to investigate associations of Fn abundance with overall survival in adjusted models.

Results

Compared to patients with undetectable or low Fn abundance, patients with high Fn abundance (n = 22) were 3-fold more likely to be diagnosed with rectal versus colon cancer (odds ratio [OR] = 3.01; 95% confidence interval [CI], 1.06-8.57; P = .04) after adjustment for patient sex, age, BMI, and study site. Patients with high Fn abundance also had a 5-fold increased risk of being diagnosed with rectal cancer versus right-sided colon cancer (OR = 5.32; 95% CI, 1.23-22.98; P = .03). There was no statistically significant association between Fn abundance and overall survival.

Conclusion

Our findings suggest that Fn abundance in fecal samples collected prior to surgery varies by tumor site among treatment-naïve CRC patients. Overall, fecal Fn abundance may have diagnostic and prognostic significance in the clinical management of CRC.

SUBMITTER: Eisele Y

PROVIDER: S-EPMC8390557 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Fusobacterium nucleatum and Clinicopathologic Features of Colorectal Cancer: Results From the ColoCare Study.

Eisele Yannick Y Mallea Patrick M PM Gigic Biljana B Stephens W Zac WZ Warby Christy A CA Buhrke Kate K Lin Tengda T Boehm Juergen J Schrotz-King Petra P Hardikar Sheetal S Huang Lyen C LC Pickron T Bartley TB Scaife Courtney L CL Viskochil Richard R Koelsch Torsten T Peoples Anita R AR Pletneva Maria A MA Bronner Mary M Schneider Martin M Ulrich Alexis B AB Swanson Eric A EA Toriola Adetunji T AT Shibata David D Li Christopher I CI Siegel Erin M EM Figueiredo Jane J Janssen Klaus-Peter KP Hauner Hans H Round June J Ulrich Cornelia M CM Holowatyj Andreana N AN Ose Jennifer J

Clinical colorectal cancer 20210227 3

<h4>Background</h4>Fusobacterium nucleatum (Fn), a bacterium associated with a wide spectrum of infections, has emerged as a key microbe in colorectal carcinogenesis. However, the underlying mechanisms and clinical relevance of Fn in colorectal cancer (CRC) remain incompletely understood.<h4>Patients and methods</h4>We examined associations between Fn abundance and clinicopathologic characteristics among 105 treatment-naïve CRC patients enrolled in the international, prospective ColoCare Study. ...[more]

PMID: 33935016

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Project description:Aspirin is a chemopreventive agent for colorectal adenoma and cancer (CRC) that, like many drugs inclusive of chemotherapeutics, has been investigated for its effects on bacterial growth and virulence gene expression. Given the evolving recognition of the roles for bacteria in CRC, in this work, we investigate the effects of aspirin with a focus on one oncomicrobe-Fusobacterium nucleatum We show that aspirin and its primary metabolite salicylic acid alter F. nucleatum strain Fn7-1 growth in culture and that aspirin can effectively kill both actively growing and stationary Fn7-1. We also demonstrate that, at levels that do not inhibit growth, aspirin influences Fn7-1 gene expression. To assess whether aspirin modulation of F. nucleatum may be relevant in vivo, we use the ApcMin/+ mouse intestinal tumor model in which Fn7-1 is orally inoculated daily to reveal that aspirin-supplemented chow is sufficient to inhibit F. nucleatum-potentiated colonic tumorigenesis. We expand our characterization of aspirin sensitivity across other F. nucleatum strains, including those isolated from human CRC tissues, as well as other CRC-associated microbes, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli Finally, we determine that individuals who use aspirin daily have lower fusobacterial abundance in colon adenoma tissues, as determined by quantitative PCR performed on adenoma DNA. Together, our data support that aspirin has direct antibiotic activity against F. nucleatum strains and suggest that consideration of the potential effects of aspirin on the microbiome holds promise in optimizing risk-benefit assessments for use of aspirin in CRC prevention and management.IMPORTANCE There is an increasing understanding of the clinical correlations and potential mechanistic roles of specific members of the gut and tumoral microbiota in colorectal cancer (CRC) initiation, progression, and survival. However, we have yet to parlay this knowledge into better CRC outcomes through microbially informed diagnostic, preventive, or therapeutic approaches. Here, we demonstrate that aspirin, an established CRC chemopreventive, exhibits specific effects on the CRC-associated Fusobacterium nucleatum in culture, an animal model of intestinal tumorigenesis, and in human colonic adenoma tissues. Our work proposes a potential role for aspirin in influencing CRC-associated bacteria to prevent colorectal adenomas and cancer, beyond aspirin's canonical anti-inflammatory role targeting host tissues. Future research, such as studies investigating the effects of aspirin on fusobacterial load in patients, will help further elucidate the prospect of using aspirin to modulate F. nucleatumin vivo for improving CRC outcomes.

Dataset Information

Fusobacterium nucleatum and Clinicopathologic Features of Colorectal Cancer: Results From the ColoCare Study.

Background

Patients and methods

Results

Conclusion

Publications

Fusobacterium nucleatum and Clinicopathologic Features of Colorectal Cancer: Results From the ColoCare Study.

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