The vaginal microbiome is associated with endometrial cancer grade and histology
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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
Hakimjavadi H, George SH, Taub M, Dodds LV, Sanchez-Covarrubias AP, Huang M, Pearson JM, Slomovitz BM, Kobetz EN, Gharaibeh R, Sowamber R, Pinto A, Chamala S, Schlumbrecht MP
Journal
Cancer research communications
Year
2022
Keywords:
Endometrial cancer, high-grade, low-grade, metagenomics, microbiome
The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
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
- Vagina Vagina,vagina,Distal oviductal region,Distal portion of oviduct,Vaginae
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Endometrial cancer cancer of endometrium,endometrial Ca,endometrial cancer,endometrial neoplasm,endometrium cancer,malignant endometrial neoplasm,malignant endometrium neoplasm,malignant neoplasm of endometrium,neoplasm of endometrium,primary malignant neoplasm of endometrium,tumor of endometrium,Endometrial cancer
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Benign
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Tumor (Low Grade + High Grade)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Tumor represents patients with low grade and high grade endometrial cancer.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 11
- Group 1 sample size Number of subjects in the case (exposed) group
- 50
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 14 days
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- BGISEQ-500 Sequencing
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- raw counts
- Statistical test
- DESeq2
- 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
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Fig. 3A
Description: Differential abundance of taxa between Tumor and Benign patients
Abundance in Group 1: increased abundance in Tumor (Low Grade + High Grade)
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridium sp. | ||
| Porphyromonas uenonis |
Revision editor(s): Prolific, KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Fig. 3A
Description: Differential abundance of taxa between Tumor and Benign patients
Abundance in Group 1: decreased abundance in Tumor (Low Grade + High Grade)
| NCBI | Quality Control | Links |
|---|---|---|
| Staphylococcus epidermidis | ||
| Streptococcus agalactiae | ||
| Winkia neuii |
Revision editor(s): KateRasheed
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High Grade
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- High Grade refers to patients with high grade endometrial cancer
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Richness Number of species
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Fig. 3B
Description: Differential abundance of taxa between High grade and Benign patients
Abundance in Group 1: increased abundance in High Grade
| NCBI | Quality Control | Links |
|---|---|---|
| Fusobacterium ulcerans |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Fig. 3B
Description: Differential abundance of taxa between High grade and Benign patients
Abundance in Group 1: decreased abundance in High Grade
Revision editor(s): KateRasheed
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Low Grade
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Low Grade refers to patients with low grade endometrial cancer
- Group 1 sample size Number of subjects in the case (exposed) group
- 30
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Fig. 3D
Description: Differential abundance of taxa between Low grade and Benign patients
Abundance in Group 1: increased abundance in Low Grade
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridium sp. | ||
| Corynebacterium amycolatum | ||
| Lactobacillus gasseri | ||
| Peptoniphilus duerdenii | ||
| Porphyromonas uenonis |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Fig. 3D
Description: Differential abundance of taxa between Low grade and Benign patients
Abundance in Group 1: decreased abundance in Low Grade
| NCBI | Quality Control | Links |
|---|---|---|
| Staphylococcus epidermidis |
Revision editor(s): KateRasheed
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low Grade
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High Grade
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- High Grade refers to patients with high grade endometrial cancer
- Group 0 sample size Number of subjects in the control (unexposed) group
- 30
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Fig. 3C
Description: Differential abundance of taxa between High grade and low grade patients
Abundance in Group 1: increased abundance in High Grade
| NCBI | Quality Control | Links |
|---|---|---|
| Prevotella bivia | ||
| Fusobacterium ulcerans |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Fig. 3C
Description: Differential abundance of taxa between High grade and low grade patients
Abundance in Group 1: decreased abundance in High Grade
Revision editor(s): KateRasheed
Experiment 5
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Benign
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Serous
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Serous histology is a term used to describe the histology of tumors, carcinomas, and other tissues that are associated with serum, the clear liquid part of blood.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 11
- Group 1 sample size Number of subjects in the case (exposed) group
- Not specified
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Supplementary Figure 5A
Description: Differential abundance of taxa between Benign and Serous
Abundance in Group 1: increased abundance in Serous
| NCBI | Quality Control | Links |
|---|---|---|
| Fusobacterium ulcerans |
Revision editor(s): KateRasheed
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Supplementary Figure 5A
Description: Differential abundance of taxa between Benign and Serous
Abundance in Group 1: decreased abundance in Serous
Revision editor(s): KateRasheed
Experiment 6
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Endometroid
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Endometrioid histology is a type of endometrial carcinoma that is the most common histological type of uterine body cancer.
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Supplementary Figure 5B
Description: Differential abundance of taxa between Benign and Endometroid
Abundance in Group 1: increased abundance in Endometroid
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus gasseri |
Revision editor(s): KateRasheed
Experiment 7
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Endometroid
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Serous
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Serous histology is a term used to describe the histology of tumors, carcinomas, and other tissues that are associated with serum, the clear liquid part of blood.
- Group 0 sample size Number of subjects in the control (unexposed) group
- Not specified
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-1-10
Source: Supplementary Figure 5C
Description: Differential abundance of taxa between Endometroid and Serous
Abundance in Group 1: decreased abundance in Serous
Revision editor(s): KateRasheed
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