Fusobacterium Nucleatum Predicts a Risk for Esophageal Squamous Cell Carcinoma

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in China. The role of the bacteria present in Esophageal squamous cell carcinoma (ESCC) tissue in neoplastic progression has not been fully elucidated. This study aimed to uncover different bacterial communities in ESCC tissues and examine the correlation between the abundance of the esophageal flora and clinical characteristics of ESCC.Method: Samples from total of 111 ESCC patients were collected, and 21 pairs of ESCC samples were analyzed by 16S rRNA sequencing. qPCR was used to verify the abundances of specific bacteria. Gene Ontology and protein domain analyses were used to analyze the whole-exome sequencing data of ESCC specimens to analyze the relationship between the abundance of the esophageal flora and signaling pathways.Results: Microorganisms in tumors and normal tissues showed obvious clustering characteristics. The abundance of Fusobacterium (P=0.0052) was increased in tumor tissues. The high level of Fusobacterium nucleatum was significantly associated with pT stage (P=0.039) and clinical stage (P=0.0039). The WES data showed that COL22A1, TRBV10-1, CSMD3, SCN7A and PSG11 were present in only the F. nucleatum-positive ESCC samples. GO and protein domain enrichment results suggested that epidermal growth factor might be involved in the regulation of cell apoptosis in F. nucleatum-positive ESCC. Both a higher mutational burden and F. nucleatum-positive was observed in tumors with metastasis than in tumors without metastasis.Conclusion: F. nucleatum is closely related to the pT stage and clinical stage of ESCC. The abundance of F. nucleatum and tumor mutation burden may be used in combination as a marker to predict metastasis in ESCC.