Intratumoral <i>Fusobacterium Nucleatum</i> Levels Predict Therapeutic Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma.

Abstract

Emerging evidence indicates that gut microbiome plays a crucial role in the cancer pathogenesis. Although <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) is associated with poor prognosis in multiple cancers, its clinical significance in predicting response to chemotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains unclear. The <i>F. nucleatum</i> levels were quantified by qPCR assays in tumor tissues from 551 patients with ESCC from two independent cohorts, including 101 patients who received neoadjuvant chemotherapy prior to curative resection. Associations between <i>F. nucleatum</i> burden and recurrence-free survival (RFS), as well with chemotherapeutic response were evaluated using response evaluation criteria in solid tumors (RECISTs), primary tumor metabolic response defined by maximum standardized uptake value (SUV_max) changes in positron emission tomography-CT (PET/CT), and pathologic tumor regression grade (TRG). High burden of <i>F. nucleatum</i> in patients with ESCC associated with poor RFS in both training [log-rank <i>P</i> = 0.02; HR = 1.61; <i>P</i> = 0.03] and validation cohorts (log-rank <i>P</i> = 0.003; HR = 1.96; <i>P</i> = 0.004). Importantly, patients with ESCC with high levels of <i>F. nucleatum</i> displayed poor chemotherapeutic response for all three evaluation methods: RECIST (<i>P</i> = 0.04), SUV_max change in PET/CT (<i>P</i> = 0.0004), and TRG (<i>P</i> = 0.003). We conclude that high levels of intratumoral <i>F. nucleatum</i> have a prognostic significance for predicting poor RFS in patients with ESCC. More importantly, our data indicates that higher <i>F. nucleatum</i> burden correlates with poor response to neoadjuvant chemotherapy, suggesting the possibility that an antibiotic intervention against this bacterium may significantly improve therapeutic response in patients with ESCC.