Feasibility of oral microbiome profiles associated with oral squamous cell carcinoma

Abstract

Objective: Recently, the possibility that oral microbiomes is associated with oral squamous cell carcinoma (OSCC) initiation and progression has attracted attention; however, this association is still unclear. Here, we comprehensively analyze the microbiome profiles of saliva samples using next-generation sequencing followed by determining the association between oral microbiome profiles and OSCC.

Materials and methods: Microbiome profiles in saliva samples from patients with OSCC, oral leukoplakia (OLK), and postoperative OSCC (Post) were analyzed. Candidate OSCC-associated bacteria were identified by comparing the bacterial diversity and relative abundance of each group based on these microbiome profiles, and their applicability as OSCC detection tools were evaluated.

Results: There were significant differences in genus abundances (Streptococcus, Aggregatibacter, and Alloprevotella) among the groups from saliva samples. In the OSCC group, compared with the OLK and Post groups, abundances of the genus Fusobacterium, phylum Fusobacteria and phylum Bacteroidetes were markedly increased and that of the genus Streptococcus and phylum Firmicutes were decreased.

Conclusion: The results suggested a strong association of these bacteria with OSCC. Especially, phylum Fusobacterium was significantly associated with early recurrence of OSCC. Thus, oral microbiome analysis may have a potential of novel OSCC detection and prognostic tool.

Keywords: Oral squamous cell carcinoma; next-generation sequencer; oral leukoplakia; oral microbiome; saliva.

Figure 1.

The results of α and β diversity analyses using QIIME scripts for oral squamous cell carcinoma (OSCC), oral leukoplakia (OLK) and post-operative of OSCC (Post) groups. Control group includes 10 healthy subjects without smoking or drinking habits or any general medical history. (a) α Diversity analysis comparing three groups and control. Analysis indices were PD whole tree, Chao1, observed species, and Shannon. (b) β diversity analysis. Analysis indices were Unweighted and Weighted Unifrac.

Figure 2.

The results of LEfSe analysis comparing between oral squamous cell carcinoma (OSCC) and non-OSCC groups (OLK, oral leukoplakia OLK: Post, post-operative of OSCC). (a) LEfSe comparison between OSCC and non-OSCC groups. (b) Top 5 bacteria of high linear discriminant analysis (LDA) for each group.

Figure 3.

A panel of bacterial markers for OSCC and non-OSCC including more than two candidate bacteria showing the different distribution of OSCC positive bacterium between each group.

Figure 4.

The result of multivariate ROC curve analysis showing a significant high AUC value in combination of four candidate bacteria when compared with g Fusobacterium alone.

Figure 5.

Kaplan-Meier curve showing recurrence within 1 year in oral squamous cell patients with high relative abundance of p Fusobacteria versus low abundance of it.