CoChat
Sign Up
Cited by 150Oral microbiology and periodontitis researchHead and Neck Cancer StudiesGut microbiota and health

The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.

Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses

Open access
Yost, Susan, Stashenko, Philip, Choi, Yoonhee, Kukuruzinska, Maria, Genco, Caroline A., Salama, Andrew, Weinberg, Ellen O., Kramer, Carolyn D., Frias-Lopez, Jorge·2018·International Journal of Oral Science
DOI 10.1038/s41368-018-0037-7PMC PMC6232154
Open this paper in CoChat — free accountOpen PDF

Abstract

Oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients. A search of the oral microbiome has revealed a group of bacteria closely associated with the most common type of oral cancer, and whose activity may play a role in its development. Oral squamous cell carcinoma (OSCC) has been linked to tobacco and alcohol consumption, but there’s increasing interest in the role bacteria might play in its initiation and growth. To better understand the behaviour of the various microbes present in the mouths of healthy people and those with OSCC, Jorge Frias-Lopez at the University of Florida in Gainesville and his colleagues carried out a metatranscriptome analysis, which identifies the most actively expressed genes. This revealed significant differences in their microbial communities, with Fusidobacteria particularly enriched and hyperactive in patients with OSCC. The team also identified microbial activities that were consistently associated with cancer.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41368-018-0037-7

Cites

73 of 73 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1 Statistical differences in the phylogenetic composition of active communities according to LEfSe. Cladograms report the taxa showing different abundance values for the transcripts (according to LEfSe). Metatranscriptome hit counts were obtained using Kraken against an oral microbiome database. Counts were then analysed using LEfSe to identify significant differences at the species level between the microbial communities compared. The alpha values were 0.05 for the Kruskal-Wallis (KW) sum-rank test and 0.01 for the Wilcoxon test. Only taxa with an LDA > 2 are represented in the cladograms. a Comparison of healthy control tumour-matched sites vs OSCC tumour sites. b Comparison of OSCC tumour-adjacent sites vs OSCC tumour sites. c Comparison of OSCC tumour-adjacent sites vs buccal sites from healthy control patients
Fig. 1 Statistical differences in the phylogenetic composition of active communities according to LEfSe. Cladograms report the taxa showing different abundance values for the transcripts (according to LEfSe). Metatranscriptome hit counts were obtained using Kraken against an oral microbiome database. Counts were then analysed using LEfSe to identify significant differences at the species level between the microbial communities compared. The alpha values were 0.05 for the Kruskal-Wallis (KW) sum-rank test and 0.01 for the Wilcoxon test. Only taxa with an LDA > 2 are represented in the cladograms. a Comparison of healthy control tumour-matched sites vs OSCC tumour sites. b Comparison of OSCC tumour-adjacent sites vs OSCC tumour sites. c Comparison of OSCC tumour-adjacent sites vs buccal sites from healthy control patientsCC BY · PubMed Central
Fig. 2 GO enrichment analysis of the metatranscriptome profiles of the oral microbiome associated with cancer status; over-represented biological processes. Enriched terms obtained using GOseq were summarised and visualised as a scatter plot using REVIGO. a Summarised GO terms in healthy control tumour-matched sites vs OSCC tumour sites. b Summarised GO terms in OSCC tumour-adjacent sites vs OSCC tumour sites. c Summarised GO terms in OSCC tumour-adjacent sites vs buccal sites from healthy control patients. Bubble size indicates the frequency of the GO term in the underlying GO database. Colour indicates the log10 P-value (red higher, green lower) showing the significance of GO enrichment for a particular GO term. The X and Y axes represent semantic spaces that have no intrinsic meaning. REVIGO uses multi-dimensional scaling to reduce the dimensionality of a matrix of the GO terms’ pairwise semantic similarities. The results with semantically similar GO terms remain close together in the plot. Semantic similarity between two GO terms is based on the shared proteins contained in those terms
Fig. 2 GO enrichment analysis of the metatranscriptome profiles of the oral microbiome associated with cancer status; over-represented biological processes. Enriched terms obtained using GOseq were summarised and visualised as a scatter plot using REVIGO. a Summarised GO terms in healthy control tumour-matched sites vs OSCC tumour sites. b Summarised GO terms in OSCC tumour-adjacent sites vs OSCC tumour sites. c Summarised GO terms in OSCC tumour-adjacent sites vs buccal sites from healthy control patients. Bubble size indicates the frequency of the GO term in the underlying GO database. Colour indicates the log10 P-value (red higher, green lower) showing the significance of GO enrichment for a particular GO term. The X and Y axes represent semantic spaces that have no intrinsic meaning. REVIGO uses multi-dimensional scaling to reduce the dimensionality of a matrix of the GO terms’ pairwise semantic similarities. The results with semantically similar GO terms remain close together in the plot. Semantic similarity between two GO terms is based on the shared proteins contained in those termsCC BY · PubMed Central
Fig. 3 Heatmaps of putative virulence factor analysis. Upregulated putative virulence factors were used for cluster analysis. a Cluster analysis of upregulated virulence factor expression profiles based on the levels of expression of specific virulence genes. b Cluster analysis of upregulated virulence factor expression profiles based on the levels of expression observed for specific species of bacteria in the biofilm. TS, OSCC tumour site; HC, healthy control tumour-matched site; TA, OSCC tumour-adjacent site; HB, buccal sites from healthy controls
Fig. 3 Heatmaps of putative virulence factor analysis. Upregulated putative virulence factors were used for cluster analysis. a Cluster analysis of upregulated virulence factor expression profiles based on the levels of expression of specific virulence genes. b Cluster analysis of upregulated virulence factor expression profiles based on the levels of expression observed for specific species of bacteria in the biofilm. TS, OSCC tumour site; HC, healthy control tumour-matched site; TA, OSCC tumour-adjacent site; HB, buccal sites from healthy controlsCC BY · PubMed Central
Fig. 4 Phylogenetic origin of upregulated putative virulence factors. Relative abundance of hits from a specific bacterium of the total differentially expressed virulence factors in each of the comparisons. a Comparison of healthy control tumour-matched sites vs OSCC tumour sites. b Comparison of OSCC tumour-adjacent sites vs OSCC tumour sites. c Comparison of OSCC tumour-adjacent sites vs buccal sites from healthy control patients
Fig. 4 Phylogenetic origin of upregulated putative virulence factors. Relative abundance of hits from a specific bacterium of the total differentially expressed virulence factors in each of the comparisons. a Comparison of healthy control tumour-matched sites vs OSCC tumour sites. b Comparison of OSCC tumour-adjacent sites vs OSCC tumour sites. c Comparison of OSCC tumour-adjacent sites vs buccal sites from healthy control patientsCC BY · PubMed Central
Fig. 5 GO enrichment analysis of the metatranscriptome profiles of Fusobacteria; over-represented biological processes. Enriched terms obtained using GOseq were summarised and visualised as a network using REVIGO. a Summarised GO terms in healthy control tumour-matched sites vs OSCC tumour sites. b OSCC tumour-adjacent sites vs OSCC tumour sites. In red are activities that are also over-represented in the oral microbiome in periodontal disease20,21
Fig. 5 GO enrichment analysis of the metatranscriptome profiles of Fusobacteria; over-represented biological processes. Enriched terms obtained using GOseq were summarised and visualised as a network using REVIGO. a Summarised GO terms in healthy control tumour-matched sites vs OSCC tumour sites. b OSCC tumour-adjacent sites vs OSCC tumour sites. In red are activities that are also over-represented in the oral microbiome in periodontal disease20,21CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 73 references

Cited by

Sorted by citations

Items 101–150 of 150

Related

See all

Metadata

Authors
Yost, S., Stashenko, P., Choi, Y., Kukuruzinska, M., Genco, C. A., Salama, A., Weinberg, E. O., Kramer, C. D., & Frias-Lopez, J.
Affiliations
  • The Forsyth Institute (US)
  • Boston University (US)
  • Tufts University (US)
ORCID
Venue
International Journal of Oral Science
Publisher
Springer Science and Business Media LLC
Published
2018-11-12
Volume
10
Issue
4
Pages
32-32
ISSN
  • 1674-2818 (ISSN-L)
  • 2049-3169
DOI
10.1038/s41368-018-0037-7
PMC
PMC6232154
OpenAlex
W2901836693
Cited by
144
References
73
Citations by year
2026: 12 · 2025: 24 · 2024: 13 · 2023: 25 · 2022: 28 · 2021: 18 · 2020: 20 · 2019: 4
FWCI
12.07
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Oral Science (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Boston University (Evans Center for Interdisciplinary Biomedical Research ARC)
  • Forsyth Institute Pilot Grant
Topics
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
oral squamous cell carcinoma, oral microbiota, metatranscriptomics, Fusobacteria, virulence factors, microbial gene expression, iron transport, tryptophanase, superoxide dismutase, capsule biosynthesis, flagellar biosynthesis, chemotaxis, hemolysin, adhesins, reactive nitrogen intermediates
MeSH terms
Carcinoma, Squamous Cell, Humans, Mouth Neoplasms, Phylogeny, Pilot Projects, RNA, Messenger, Virulence, Virulence Factors, Metagenome, Transcriptome, Microbiota

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review