The vaginal microbiome is associated with endometrial cancer grade and histology

Study information

Needs review

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

35928983

DOI Digital object identifier for electronic documents.

https://doi.org/10.1158/2767-9764.CRC-22-0075

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

Edit History Delete

Mark reviewed

Your review change was submittedDuplicate this Experiment Add a new Signature

Needs review

Curated date: 2024/11/21

Curator: Prolific

Revision editor(s): Prolific

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: Vaginal fluid Vaginal discharge,Vaginal secretion,Vaginal fluid,vaginal fluid

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Uterine cancer CA - cancer of uterus,cancer of the uterus,cancer of uterus,malignant neoplasm of the uterus,malignant neoplasm of uterus,malignant tumor of the uterus,malignant tumor of uterus,malignant uterine neoplasm,malignant uterine tumor,malignant uterus neoplasm,neoplasm of uterus,tumour of uterus,uterine cancer,uterine tumor,uterus cancer,uterus neoplasm,Uterine cancer

Group 0 name Corresponds to the control (unexposed) group for case-control studies: HPV-negative group

Group 1 name Corresponds to the case (exposed) group for case-control studies: HPV- positive with persistent infection group

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Women who showed persistent high-risk HPV infection across two or more consecutive visits.

Group 1 sample size Number of subjects in the case (exposed) group: 80

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: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: Kruskall-Wallis; 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

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Matched on Factors on which subjects have been matched on in a case-control study: age, body mass index, race, sexual preference

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: antibiotic exposure, sexual preference

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: increased

Simpson Estimator of species richness and species evenness: more weight on species evenness: increased

Signature 1

Edit History Delete

incomplete

Curated date: 2024/11/21

Curator: Prolific

Revision editor(s): Prolific

Source: Figure 3

Description: significant changes in microbial taxa associated with HPV-positive and HPV-negative groups.

Abundance in Group 1: increased abundance in HPV- positive with persistent infection group

NCBI	Quality Control	Links

Revision editor(s): Prolific