Abstract

The relationship between oral squamous cell carcinoma (OSCC) development and the microbiome has attracted increasing attention. The depth of invasion (DOI) is an important indicator of tumor progression, staging and prognosis, and the change in the oral microbiome based on the DOI is unclear. This report describes the use of metagenomic analyses to investigate the relationship between the oral microbiome and the DOI. Forty patients in different DOI categories were recruited; 10 healthy people served as the control group. Swab samples collected from the participants were subjected to metagenomic analyses, and the oral microbial communities and their functions were investigated. The abundances of Fusobacterium nucleatum, Capnocytophaga sputigena, Porphyromonas endodontalis, and Gemella haemolysans were significantly increased in the patients compared with the controls. The abundances of some bacteria exhibited a stage-related trend. The abundances of P. endodontalis, Gemella morbillorum and G. haemolysans increased with increasing DOI. In contrast, the abundances of Prevotella melaninogenica, Haemophilus parainfluenzae and Neisseria flavescens decreased with increasing DOI. Based on receiver operating characteristic (ROC) curve analysis, eight species were found to have predictive value: Rothia mucilaginosa, P. melaninogenica, H. parainfluenzae, and N. flavescens in the healthy control group and P. endodontalis, G. morbillorum, G. haemolysans and Fusobacterium periodonticum in the high DOI group. In the functional analysis, several metabolic pathways were decreased, whereas flagellar assembly and bacterial chemotaxis showed an increasing trend as the disease progressed. Biofilm formation, flagella, lipopolysaccharide (LPS) and other virulence factors exhibited staging-related changes. These pathogenic pathways and factors had a clear correlation with specific pathogens. In particular, when OSCC progressed to the late stage, microbial diversity and functional potential changed greatly.

Highlights

  • In 2017, the 8th edition of the Union for International Cancer Control and American Joint Committee on Cancer staging manual incorporated tumor depth of invasion (DOI) in the T category of the TNM staging system for oral squamous cell carcinoma (OSCC) (Amin et al, 2017; Brierley et al, 2017)

  • We described the bacterial diversity and functional transitions associated with the DOI

  • We explored the functional features of the oral microbiome across the four groups in our study by annotating the gene catalog based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) modules

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Summary

Introduction

In 2017, the 8th edition of the Union for International Cancer Control and American Joint Committee on Cancer staging manual incorporated tumor depth of invasion (DOI) in the T category of the TNM (tumor, node, metastasis) staging system for oral squamous cell carcinoma (OSCC) (Amin et al, 2017; Brierley et al, 2017). Recent research has shown that some microbes promote carcinogenesis, such as Helicobacter pylori, which promotes the development of cancer through epithelial injury and inflammation (Smoot, 1997). Other research has indicated that cancers can be promoted by dysbiotic microbiomes (Schwabe and Jobin, 2013); for instance, disorders of intestinal microorganisms can promote colorectal cancer. The composition and function of bacteria in OSCC deserve attention because they may play an important role in the development of cancer

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