摘要
BACKGROUND An increased amount of Fusobacterium nucleatum(F.nucleatum)is frequently detected in the gastric cancer-associated microbiota of the Taiwan Residents 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 tha
基金
by Chiayi Chang Gung Memorial Hospital grants,including No.CORPG6G0021,No.CORPG6G0022 and No.CORPG6G0023 to Wu CS
No.CORPG6G0061,No.CORPG6G0062 and No.CORPG6G0063 to Tung SY
No.CORPG6G0071,No.CORPG6G0072 and No.CORPG6G0073 to Hsieh YY.
