Tumor-Intrinsic Microbiome-Based Subtyping of Esophageal Cancer as Predictive Biomarkers for Postoperative Survival.

Abstract

This study aims to investigate the impact of different treatment regimens on the intratumoral microbiota (ITM) composition in esophageal cancer patients and its association with prognosis. Tumor tissue samples from 107 esophagectomy patients were analyzed by using 5R 16S rRNA sequencing. Patients were classified into esophagotype A and B via hierarchical clustering, and the relationship between microbiota and prognosis was assessed through Kaplan-Meier survival analysis and Cox regression. Significant differences in ITM diversity and composition were observed between the neoadjuvant chemoimmunotherapy (nCIT) and surgery alone groups. Esophagotype A was enriched with Firmicutes and Lactobacillus, while esophagotype B with Proteobacteria and Fusobacterium. Survival analysis revealed that patients with esophagotype B had significantly worse outcomes compared with esophagotype A. The 3- and 5-year overall survival rates for esophagotype A were 73 and 69.2%, respectively, significantly higher than those for esophagotype B (57 and 37.5%; p < 0.05 and p < 0.01, respectively). Similarly, the 3- and 5-year recurrence-free survival rates for esophagotype A were both 80.7% compared with 64 and 50.1% for esophagotype B. Multivariable Cox regression confirmed microbial clustering within esophageal cancer subtypes as an independent prognostic factor. This study classifies esophageal cancer based on ITM signatures, highlighting the microbiota's prognostic significance and supporting the potential of microbiome-based strategies for personalized treatment.