Abstract
Abstract
Oral squamous cell carcinoma (OSCC) is a complex malignancy representing 90% of all oral cancers having its origin from mucosal epithelium. The progression of cancer is associated with multiple factors such as social habits, environmental, genetic alterations, poor oral health, viral or chronic bacterial infections. It involves the step-wise transition from normal epithelia to pre-malignant lesions to metastatic tumor. The mucosal-associated bacterial infections and chronic inflammation are implicated in OSCC pathogenesis. Alterations to the integrity of epithelial barrier initiate polymicrobial infections by shifting the indigenous commensals to opportunistic pathogens. We hypothesize that specific bacteria colonize epithelial dysplasia and OSCC site. We investigated the dysbiosis in complex oral microbial communities present at dysplasia and tumor sites as compared to non-diseased sites using high throughput pyrosequencing. Bacterial genomic DNA was purified from the brush biopsy samples of 11 patients with epithelial dysplasia and from the tissue samples of 18 patients with OSCC along with its corresponding non-dysplasia and non-tumor controls collected ∼5cm distant to lesion or contralaterally. PCR amplicons targeting V3-V5 region of 16S rRNA gene were sequenced by 454 pyrosequencing. The bacterial community structures were evaluated using QIIME analysis pipeline. Phylum Firmicutes and genus Streptococcus was found to be predominant in all non-diseased and diseased oral sites. Bacteroidetes and Fusobacteria were elevated at tumor sites as compared to non-tumor controls, dysplasia and non-dysplasia controls. Genera, Actinomyces, unclassified Methylobacteriaceae, unclassified Comamonadaceae and Acenitobacter were prevalent in dysplasia site (p<0.1) as compared to non-dysplastic site. Rothia and Parascardovia were higher in dysplasia samples whereas Prevotella, Capnocytophaga, unclassified Clostridiaceae, Fusobacteria and Wolbachia showed higher frequency in tumor samples. Thirty eight named species-level OTUs were common to all four sites suggesting the co-existence of this microbiota with their specific environment. The species richness was higher in tumor samples which reflect more diverse bacterial communities in OSCC lesions. ß-diversity showed that most of the bacterial communities were similar within the site with some overlap between the sites signifying altered microbiome. The dysbiosis in the bacterial community structure from non-diseased sites to dysplasia to tumor sites may indicate site specificity of certain bacteria to colonize OSCC and dysplasia lesions. These bacteria can prove to be the potential targets for further studies. This work is supported by grants DE019178 and DE020891.
Citation Format: Deepak Saxena, Smruti Pushalkar, Arun Devotta, Yihong Li, Bhuvanesh Singh, Zoya Kurago Kurago, Alexander Kerr, Wenbo Yan, Peter Sacks, Xin Li. Microbiome in Oral Epithelial Dysplasia and Squamous Cell Carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4834. doi:10.1158/1538-7445.AM2014-4834