Fusobacterium nucleatum-triggered purine metabolic reprogramming drives tumorigenesis in head and neck carcinoma.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is a vital pro-oncogenic bacterium. Our previous study revealed that a high abundance of F. nucleatum in head and neck squamous cell carcinoma (HNSCC) is correlated with poor patient prognosis. However, the impact of F. nucleatum on metabolic reprogramming and tumor progression in HNSCC awaits more exploration. METHODS: Liquid chromatography‒mass spectrometry (LC‒MS) was applied to analyze the altered metabolites in a head and neck carcinoma cell line (AMC-HN-8) after coculture with F. nucleatum for 24 hrs and 48 hrs. Both univariate and multivariate analyses were used to screen for differential metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment analysis was further used to explore the metabolic changes. RESULTS: We observed a significantly altered metabolic profile in AMC-HN-8 cells over time after coculture with F. nucleatum. Among the several enriched pathways, the purine metabolic pathway was the most significantly enriched (P = 0.0005), with downregulation of purine degradation. Furthermore, uric acid, the end product of purine metabolism, significantly reversed F. nucleatum-triggered tumor progression and altered the intracellular reactive oxygen species (ROS) level. Moreover, the negative correlation between the serum uric acid level and the abundance of F. nucleatum was verified in 113 HNSCC patients (P = 0.0412, R = - 0.1924). CONCLUSIONS: Our study revealed obviously aberrant purine metabolism driven by F. nucleatum in HNSCC, which was closely related to tumor progression and patient prognosis. These findings indicate the possibility of targeting F. nucleatum-induced purine metabolism reprogramming in the future treatment of HNSCC.