The oral microbiome is associated with the diagnosis, prognosis and radiotherapy sensitivity of esophageal cancer

Esophageal cancer (EC) is a leading cause of cancer-related mortality worldwide and early detection strategies and precise postoperative interventions must be developed. However, the identification of noninvasive biomarkers for the diagnosis and prognosis remains limited.

We performed 16S rRNA gene sequencing on tongue-coating samples from 440 participants, including 157 EC patients, 167 healthy controls (HCs) and 120 EC patients who received radiotherapy. We characterized the oral microbiome and constructed microbial diagnostic and prognostic classifiers. Furthermore, the oral microbiome of EC who received radiotherapy (n = 120) was characterized.

The oral microbial diversity of EC patients was increased, with differences in the microbial community between EC patients and HCs. In EC, the genera Veillonella, Streptococcus and Actinomyces were enriched, whereas Porphyromonas and Rothia were depleted. The classifier based on six optimal microbial markers was constructed using random forest algorithm and achieved area under the curves (AUCs) of 93.69% and 95.18% in discovery and validation groups, respectively. After radiotherapy, the oral microbial diversity and richness were significantly reduced. The prevalence of opportunistic pathogens, including Fusobacterium and Porphyromonas, decreased, whereas the prevalence of Streptococcus and Actinomyces increased in EC patients after radiotherapy. Through six months of follow-up, patients were categorized into a progression group (PG) (n = 26) and a nonprogression group (NPG) (n = 106) based on the presence of tumor recurrence, metastasis, and death. A prognostic model based on 13 selected amplicon sequence variants (ASVs) of the oral microbiome was constructed, with an AUC of 99.29%. The random forest analysis identified six key differential ASVs between the PG and the NPG, including Fusobacterium and Gemella. Additionally, twenty-five ASVs associated with nine clinical indicators were identified.

Our study provides a comprehensive characterization of the oral microbiome in both EC patients and EC patients after radiotherapy, highlighting the potential of the oral microbiome as noninvasive biomarkers for determining the diagnosis and prognosis of EC.