Tissue-resident microbiota signature in nasopharyngeal carcinoma.

Abstract

Background: Emerging evidence reveals that microbiota plays a crucial role in multiple cancers. Nasopharyngeal carcinoma (NPC) tissues harbour microbiota, highlighting the need to investigate the clinical implications of tissue-resident microbiota in the development of NPC. Here, we aim to clarify the specific profile of tissue-resident microbiota and its influence on NPC outcomes.

Results: This retrospective study included 491 NPC patients from Sun Yat-sen University Cancer Center (Guangzhou, China) and the Affiliated Hospital of Guilin Medical College (Guilin, China). We profiled the microbial composition of 343 NPC and 36 normal nasopharyngeal tissues through sequencing of the genes encoding the 16S rRNA subunit of bacterial ribosomes. There were significant differences in microbial composition, alpha diversity (Shannon index, P = 0.007; Simpson index, P = 0.036), and beta diversity (Bray-Curtis distance: R² = 0.016, F = 5.187, P = 0.001; unweighted UniFrac distance: R² = 0.017, F = 5.373, P = 0.001) between NPC and normal nasopharyngeal tissues. A bacterial signature comprising four risk bacterial genera, including Bacteroides, Alloprevotella, Parvimonas, and Dialister, was constructed in the training cohort (n = 171). Patients in the high-risk group had shorter disease-free (HR 2.80, 95% CI 1.51-5.18, P < 0.001), distant metastasis-free (HR 4.00, 95% CI 1.77-9.01, P < 0.001), and overall survival (HR 3.45, 95% CI 1.77-6.72, P < 0.001) than those of patients in the low-risk group. Similar results were yielded in the internal validation (n = 172) and external validation (n = 148) cohorts. Integrated multi-omics analysis revealed that NPC tissues harbouring abundant risk bacteria were characterised by deficient immune infiltration, which was verified by multiplex immunohistochemistry.

Conclusions: This study developed and validated the applicability of a four-bacteria signature as a prognostic tool for NPC prognostication. Integrated multi-omics analysis further uncovered that the tumour immune microenvironment was perturbed by tissue-resident microbiota, which might pave the way towards the era of microbiota-targeted precision medicine for NPC. Video Abstract.