BACKGROUND
An increased amount of
Fusobacterium nucleatum
(
F. nucleatum
) is frequently detected in the gastric cancer-associated microbiota of the Taiwanese population.
F. nucleatum
is known to exert cytotoxic effects and play a role in the progression of colorectal cancer, though the impact of
F. nucleatum
colonization on gastric cancer cells and patient prognosis has not yet been examined.
AIM
To identify
F. nucleatum-
dependent molecular pathways in gastric cancer cells and to determine the impact of
F. nucleatum
on survival in gastric cancer.
METHODS
Coculture of
F. nucleatum
with a gastric cancer cell line was performed, and changes in gene expression were investigated. Genes with significant changes in expression were identified by RNA sequencing. Pathway analysis was carried out to determine deregulated cellular functions. A cohort of gastric cancer patients undergoing gastrectomy was recruited, and nested polymerase chain reaction was performed to detect the presence of
F. nucleatum
in resected cancer tissues. Statistical analysis was performed to determine whether
F. nucleatum
colonization affects patient survival.
RESULTS
RNA sequencing and subsequent pathway analysis revealed a drastic interferon response induced by a high colonization load. This response peaked within 24 h and subsided after 72 h of incubation. In contrast, deregulation of actin and its regulators was observed during prolonged incubation under a low colonization load, likely altering the mobility of gastric cancer cells. According to the clinical specimen analysis, approximately one-third of the gastric cancer patients were positive for
F. nucleatum
, and statistical analysis indicated that the risk for colonization increases in late-stage cancer patients. Survival analysis demonstrated that
F. nucleatum
colonization was associated with poorer outcomes among patients also positive for
Helicobacter pylori
(
H. pylori
).
CONCLUSION
F. nucleatum
colonization leads to deregulation of actin dynamics and likely changes cancer cell mobility. Cohort analysis demonstrated that
F. nucleatum
colonization leads to poorer prognosis in
H. pylori-
positive patients with late-stage gastric cancer. Hence, combined colonization of
F. nucleatum
and
H. pylori
is a predictive biomarker for poorer survival in late-stage gastric cancer patients treated with gastrectomy.