Microbiomic differences in tumor and paired-normal tissue in head and neck squamous cell carcinomas
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Wang H, Funchain P, Bebek G, Altemus J, Zhang H, Niazi F, Peterson C, Lee WT, Burkey BB, Eng C
Journal
Genome medicine
Year
2017
Keywords:
Bacteria, Head and neck squamous cell carcinoma (HNSCC), Microbiome
BACKGROUND: While the role of the gut microbiome in inflammation and colorectal cancers has received much recent attention, there are few data to support an association between the oral microbiome and head and neck squamous cell carcinomas. Prior investigations have been limited to comparisons of microbiota obtained from surface swabs of the oral cavity. This study aims to identify microbiomic differences in paired tumor and non-tumor tissue samples in a large group of 121 patients with head and neck squamous cell carcinomas and correlate these differences with clinical-pathologic features. METHODS: Total DNA was extracted from paired normal and tumor resection specimens from 169 patients; 242 samples from 121 patients were included in the final analysis. Microbiomic content of each sample was determined using 16S rDNA amplicon sequencing. Bioinformatic analysis was performed using QIIME algorithms. F-testing on cluster strength, Wilcoxon signed-rank testing on differential relative abundances of paired tumor-normal samples, and Wilcoxon rank-sum testing on the association of T-stage with relative abundances were conducted in R. RESULTS: We observed no significant difference in measures of alpha diversity between tumor and normal tissue (Shannon index: p = 0.13, phylogenetic diversity: p = 0.42). Similarly, although we observed statistically significantly differences in both weighted (p = 0.01) and unweighted (p = 0.04) Unifrac distances between tissue types, the tumor/normal grouping explained only a small proportion of the overall variation in the samples (weighted R2 = 0.01, unweighted R2 < 0.01). Notably, however, when comparing the relative abundances of individual taxa between matched pairs of tumor and normal tissue, we observed that Actinomyces and its parent taxa up to the phylum level were significantly depleted in tumor relative to normal tissue (q < 0.01), while Parvimonas was increased in tumor relative to normal tissue (q = 0.01). These differences were more pronounced among patients with more extensive disease as measured by higher T-stage. CONCLUSIONS: Matched pairs analysis of individual tumor-normal pairs revealed significant differences in relative abundance of specific taxa, namely in the genus Actinomyces. These differences were more pronounced among patients with higher T-stage. Our observations suggest further experiments to interrogate potential novel mechanisms relevant to carcinogenesis associated with alterations of the oral microbiome that may have consequences for the human host.
Experiment 1
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Oral cavity Bucca,Buccal cavity,Cavity of mouth,Oral cavity,oral cavity
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Head and neck squamous cell carcinoma carcinoma of the head and neck,craniocervical region squamous cell carcinoma,head and neck squamous cell carcinoma,HNSCC,SCCHN,squamous cell carcinoma of head and neck,squamous cell carcinoma of the head and neck,squamous cell carcinoma, head and neck,squamous cell carcinomas of head and neck,Head and neck squamous cell carcinoma
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- normal adjacent tissues
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- squamous cell carcinoma tissues
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- tissues with evidence of squamous cell carcinoma
- Group 0 sample size Number of subjects in the control (unexposed) group
- 121
- Group 1 sample size Number of subjects in the case (exposed) group
- 121
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V1-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Sanger
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Source: Figure 3 +text
Description: Significant taxa by Wilcoxon signed-rank in paired tumor and normal tissue. Box plots representing relative abundances of taxa observed to be significantly different between tumor (orange) and adjacent normal (blue) samples by paired Wilcoxon signed-rank testing after correction for FDR.
Abundance in Group 1: increased abundance in squamous cell carcinoma tissues
| NCBI | Quality Control | Links |
|---|---|---|
| Tissierellaceae | ||
| Parvimonas |
Revision editor(s): WikiWorks
Signature 2
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Source: Figure 3 +text
Description: Significant taxa by Wilcoxon signed-rank in paired tumor and normal tissue. Box plots representing relative abundances of taxa observed to be significantly different between tumor (orange) and adjacent normal (blue) samples by paired Wilcoxon signed-rank testing after correction for FDR.
Abundance in Group 1: decreased abundance in squamous cell carcinoma tissues
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Actinomycetes | ||
| Actinomycetales | ||
| Actinomycetaceae | ||
| Actinomyces |
Revision editor(s): WikiWorks
Experiment 2
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- T0-T2 low tumor stages patients
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- T3-T4 high tumor stages patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Not stated
- Group 0 sample size Number of subjects in the control (unexposed) group
- Not specified
- Group 1 sample size Number of subjects in the case (exposed) group
- Not specified
Lab analysis
Statistical Analysis
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Signature 1
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Source: Figure 4 +text
Description: Relative abundances of differentially represented taxa stratified by T-stage. Box plots representing relative abundances of phylum Actinobacteria (top), genus Actinomyces (middle), and genus Parvimonas (bottom) stratified by T-stage.
Abundance in Group 1: increased abundance in T3-T4 high tumor stages patients
| NCBI | Quality Control | Links |
|---|---|---|
| Parvimonas |
Revision editor(s): WikiWorks
Signature 2
Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
Source: Figure 4 +text
Description: Relative abundances of differentially represented taxa stratified by T-stage. Box plots representing relative abundances of phylum Actinobacteria (top), genus Actinomyces (middle), and genus Parvimonas (bottom) stratified by T-stage.
Abundance in Group 1: decreased abundance in T3-T4 high tumor stages patients
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomyces | ||
| Actinomycetota |
Revision editor(s): WikiWorks
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