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F. nucleatum associated with poor survival in esophageal cancer
The presence of Fusobacterium nucleatum in cancer tissue appeared associated with shorter survival in patients with esophageal cancer, according to results of a study conducted in Japan.
“F. nucleatum, a nonspore-forming, anaerobic gram–negative bacterium, is part of the normal flora in the human oral cavity, vagina and gastrointestinal mucosa. It is recognized as a pathogen in periodontal diseases, chorioamnionitis and inflammatory bowel disease,” Kensuke Yamamura, PhD, of the department of gastroenterological surgery at Kumamoto University in Japan, and colleagues wrote. “[Previous] studies reported that high levels of F. nucleatum DNA were linked to a poor prognosis in human cancers, whereas others reported no association between F. nucleatum DNA levels and patient survival. However, no studies to date have examined the prognostic impact of F. nucleatum in esophageal cancer tissues.”
Researchers analyzed formalin-fixed, paraffin-embedded esophageal cancers in 325 patients who underwent tumor resection at Kumamoto University Hospital between April 2005 and June 2013. Yamamura and colleagues observed patients whose specimens contained F. nucleatum at 1- to 3-month intervals until either Jan. 31, 2016, or patient death.
Three hundred (92%) cases were diagnosed as squamous cell carcinoma, whereas 12 (3.7%) were diagnosed as adenocarcinoma and 13 (4%) were diagnosed as other types of cancer. A total of 117 patients underwent preoperative treatment.
The researchers detected F. nucleatum in 74 (23%) cases and reported that cancer tissues had significantly greater amounts of F. nucleatum DNA than matched healthy esophageal mucosa (n = 60; P = .021). Median F. nucleatum DNA content in cancer tissues was 2.3 x 10–2 (range, 3 x 10–4 to 2.8 x 100).
The presence of F. nucleatum DNA was associated with cancer-specific survival (univariate HR = 2.01; 95% CI, 1.22-3.23; multivariate HR = 1.78; 95% CI, 1.06-2.94). Positivity for F. nucleatum was associated with tumor stage (P = .016), T stage (P < .01) and N stage (P = .039), but not sex, age, year of operation, alcohol or smoking history, tumor location, histology, comorbidity or preoperative therapy.
“F. nucleatum was detected in esophageal cancer tissues and was associated with short survival,” Yamamura and colleagues wrote. “F. nucleatum might also contribute to the acquisition of aggressive tumor behavior through the activation of chemokines, such as CCL20.” – by Andy Polhamus
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Christopher Fundakowski, MD
Patients and clinicians alike are continually searching for ways to identify who will develop cancer, which cancers will be most aggressive, and who will best respond to treatment. Interestingly, the role of the human microbiome as it relates to development of systemic disease and malignancy is becoming of increasing importance. In a study by Yamamura and colleagues, patients with esophageal cancer who were found to have a specific type of bacteria within the tumor had worse prognosis. Fusobacterium nucleatum is commonly found in the oral cavity and is known to cause periodontal disease. In the study, F. nucleatum was found more often in esophageal tumors than in the adjacent normal tissues, suggesting a possible role in tumorigenesis. Of those patients with F. nucleatum DNA identified in the tumor, survival was shorter compared with those who lacked this bacteria. These bacteria also appear to be involved in cell signaling through an activation of a chemokine known as CCL20. Given the findings, it is suggested that the presence of F. nucleatum in esophageal cancer specimens may serve as a prognostic biomarker in the future. Many important questions arise from this investigation that will prompt additional studies and hopefully impact clinical practice, such as: Why is the bacteria not present in all tumors and what is unique about these patients? Is there a way to eliminate these bacteria from the oral cavity or aerodigestive tract and, if so, will it have an impact on the development or behavior of esophageal cancer? What other subtypes of cancer are affected by the presence of this bacteria or other bacteria yet to be studied? We likely have just scratched the surface of the importance and implications of the human microbiome as it relates to tumor development and behavior.
Christopher Fundakowski, MD
Department of Surgical Oncology
Fox Chase Cancer Center, Philadelphia, PA
Disclosure: Fundakowski reports no relevant financial disclosures.