Compositional and Functional Differences between Microbiota and Cervical Carcinogenesis as Identified by Shotgun Metagenomic Sequencing

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/1

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

30841606

DOI Digital object identifier for electronic documents.

10.3390/cancers11030309

URI

Authors

Kwon M, Seo SS, Kim MK, Lee DO, Lim MC

Journal

Cancers

Year

2019

Keywords:

cervical cancer, cervical intraepithelial neoplasia, microbiome, shotgun metagenomic sequencing

Recent studies have reported the potential role of microbiomes in cervical disease. However, little is known about the microbiome composition and function in cervical carcinogenesis. We aimed to identify the compositional and functional alterations of cervical microbiomes in cases of cervical carcinogenesis of Korean women using shotgun metagenomic sequencing. In this study, using shotgun sequencing, we sequenced the cervical metagenomes of cervical intraneoplasia 2/3 (n = 17), cervical cancer (n = 12), and normal controls (n = 18) to identify the microbial abundances and enriched metabolic functions in cervical metagenomes. At the genus level, the microbiota of cervical cancer were differentially enriched with genera Alkaliphilus, Pseudothermotoga, and Wolbachia. Cervical intraepithelial neoplasia (CIN) 2/3 were enriched with Lactobacillus, Staphylococcus, and Candidatus Endolissoclinum. The normal group was enriched with Pseudoalteromonas and Psychrobacter. Further characterization of the functionalities of the metagenomes may suggest that six Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) that are involved in 10 pathways are associated with an increased risk of CIN2/3 and cervical cancer. Specifically, cervical metagenomes were enriched in the course of peptidoglycan synthesis and depleted by dioxin degradation and 4-oxalocrotonate tautomerase. The Cluster of Orthologous Groups (COG) category 'Defense mechanisms' was depleted in cervical cancer patients. Our findings based on shotgun metagenomic sequencing suggest that cervical microbiome community compositions and their metagenomics profiles differed between cervical lesions and normal subjects. Future studies should have larger sample sizes and/or aggregate their results to have sufficient power to detect reproducible and significant associations.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/1

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Cynthia Anderson, Claregrieve1, WikiWorks, Peace Sandy

Subjects

Location of subjects: South Korea

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: Uterine cervix Canalis cervicis uteri,Caudal segment of uterus,Cervical canal,Cervical canal of uterus,Cervix,Cervix of uterus,Cervix uteri,Neck of uterus,Uterine cervix,uterine cervix

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Cervical glandular intraepithelial neoplasia Cervical glandular intraepithelial neoplasia,cervical glandular intraepithelial neoplasia

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

Group 1 name Corresponds to the case (exposed) group for case-control studies: cervical intraepithelial neoplasia cases

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: women with histology proven CIN2/3

Group 0 sample size Number of subjects in the control (unexposed) group: 18

Group 1 sample size Number of subjects in the case (exposed) group: 17

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: Illumina

Statistical Analysis

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

Statistical test: LEfSe

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: 2.5

Alpha Diversity

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

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

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/1

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): LGeistlinger, Cynthia Anderson, WikiWorks

Source: Figure 1

Description: Microbial compositions among normal group, cervical intraepithelial neoplasia 2 or 3, and cervical cancer

Abundance in Group 1: increased abundance in cervical intraepithelial neoplasia cases

NCBI	Quality Control	Links
Alkaliphilus
Pseudothermotoga
Wolbachia

Revision editor(s): LGeistlinger, Cynthia Anderson, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/1

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Figure 1

Description: Microbial compositions among normal group, cervical intraepithelial neoplasia 2 or 3, and cervical cancer

Abundance in Group 1: decreased abundance in cervical intraepithelial neoplasia cases

NCBI	Quality Control	Links
Pseudoalteromonas
Psychrobacter

Revision editor(s): WikiWorks

Experiment 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/1

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Cynthia Anderson, Claregrieve1, WikiWorks

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Cervical cancer cancer of uterine cervix,cervical neoplasm,cervix cancer,cervix uteri cancer,malignant cervical neoplasm,malignant cervical tumor,malignant cervix neoplasm,malignant cervix tumor,malignant cervix uteri neoplasm,malignant cervix uteri tumor,malignant neoplasm of cervix,malignant neoplasm of cervix uteri,malignant neoplasm of the cervix,malignant neoplasm of the cervix uteri,malignant neoplasm of the uterine cervix,malignant neoplasm of uterine cervix,malignant tumor of cervix,malignant tumor of cervix uteri,malignant tumor of the cervix,malignant tumor of the cervix uteri,malignant tumor of the uterine cervix,malignant tumor of uterine cervix,malignant uterine cervix neoplasm,malignant uterine cervix tumor,tumor of the cervix uteri,uterine cervical neoplasm,uterine cervix cancer,Cervical cancer,cervical cancer

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

Group 1 name Corresponds to the case (exposed) group for case-control studies: cervical cancer

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: histology proven cervical cancer

Group 1 sample size Number of subjects in the case (exposed) group: 12

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: Not specified