Research Papers:

Bacteriome and mycobiome associations in oral tongue cancer

Pranab K. Mukherjee, Hannah Wang, Mauricio Retuerto, Huan Zhang, Brian Burkey, Mahmoud A. Ghannoum and Charis Eng _

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Oncotarget. 2017; 8:97273-97289. https://doi.org/10.18632/oncotarget.21921

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Pranab K. Mukherjee1,*, Hannah Wang2,3,*, Mauricio Retuerto1, Huan Zhang2,3, Brian Burkey4,7, Mahmoud A. Ghannoum1,7,8 and Charis Eng2,3,4,6,8

1Center for Medical Mycology, Department of Dermatology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

2Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

3Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA

4Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

5Section of Head and Neck Surgery and Oncology, Head and Neck Institute, Cleveland Clinic, Cleveland, OH, USA

6Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA

7Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA

8Germline High Risk Cancer Focus Group, CASE Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA

*Contributed equally to the work and should be viewed as joint first authors

Correspondence to:

Charis Eng, email: [email protected]

Mahmoud A. Ghannoum, email: [email protected]

Keywords: microbiome; metagenomics; head and neck squamous cell carcinoma; lingual carcinomas

Received: June 08, 2017    Accepted: September 08, 2017    Published: October 19, 2017


Squamous cell carcinoma of the oral (mobile) tongue (OMTC), a non-human papilloma virus-associated oral cancer, is rapidly increasing without clear etiology. Poor oral hygiene has been associated with oral cancers, suggesting that oral bacteriome (bacterial community) and mycobiome (fungal community) could play a role. While the bacteriome is increasingly recognized as an active participant in health, the role of the mycobiome has not been studied in OMTC. Tissue DNA was extracted from 39 paired tumor and adjacent normal tissues from patients with OMTC. Microbiome profiling, principal coordinate, and dissimilarity index analyses showed bacterial diversity and richness, and fungal richness, were significantly reduced in tumor tissue (TT) compared to their matched non-tumor tissues (NTT, P<0.006). Firmicutes was the most abundant bacterial phylum, which was significantly increased in TT compared to NTT (48% vs. 40%, respectively; P=0.004). Abundance of Bacteroidetes and Fusobacteria were significantly decreased in TT compared to matched NTT (P≤0.003 for both). Abundance of 22 bacterial and 7 fungal genera was significantly different between the TT and NTT, including Streptococcus, which was the most abundant and significantly increased in the tumor group (34% vs. 22%, P<0.001). Abundance of fungal genus Aspergillus in TT correlated negatively with bacteria (Actinomyces, Prevotella, Streptococcus), but positively with Aggregatibacter. Patients with high T-stage disease had lower mean differences between TT and NTT compared with patients with low T-stage disease (0.07 vs. 0.21, P=0.04). Our results demonstrate differences in bacteriome and mycobiome between OMTC and their matched normal oral epithelium, and their association with T-stage.

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