Fusobacteria alterations are associated with colorectal cancer liver metastasis and a poor prognosis

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Reviewed Marked as Reviewed by Svetlana up on 2024-6-3
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Jin M, Fan Q, Shang F, Zhang T, Ogino S, Liu H
Journal
Oncology letters
Year
2024
Keywords:
colorectal cancer, fusobacteria, gut microbiota, liver metastasis
Liver metastasis is a major cause of mortality in patients with advanced stages of colorectal cancer (CRC). The gut microbiota has been demonstrated to influence the progression of liver diseases, potentially providing novel perspectives for diagnosis, treatment and research. However, the gut microbial characteristics in CRC with liver metastasis (LM) and with no liver metastasis (NLM) have not yet been fully established. In the present study, high-throughput 16S RNA sequencing technology was employed, in order to examine the gut microbial richness and composition in patients with CRC with LM or NLM. A discovery cohort (cohort 2; LM=18; NLM=36) and a validation cohort (cohort 3; LM=13; NLM=41) were established using fresh feces. In addition, primary carcinoma tissue samples were also analyzed (LM=8 and NLM=10) as a supplementary discovery cohort (cohort 1). The findings of the present study indicated that the intestinal microbiota richness and diversity were increased in the LM group as compared to the NLM group. A significant difference was observed in species composition between the LM and NLM group. In the two discovery cohorts with two different samples, the dominant phyla were consistent, but varied at lower taxonomic levels. Phylum Fusobacteria presented consistent and significant enrichment in LM group in both discovery cohorts. Furthermore, with the application of a random forest model and receiver operator characteristic curve analysis, Fusobacteria was identified as a potential biomarker for LM. Moreover, Fusobacteria was also a poor prognosis factor for survival. Importantly, the findings were reconfirmed in the validation cohort. On the whole, the findings of the present study demonstrated that CRC with LM and NLM exhibit distinct gut microbiota characteristics. Fusobacteria detection thus has potential for use in predicting LM and a poor prognosis of patients with CRC.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-6-3

Curated date: 2024/04/19

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Subjects

Location of subjects
China
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
Colorectum Colorectum,colorectum
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Metastatic colorectal cancer Metastatic colorectal cancer,metastatic colorectal cancer
Group 0 name Corresponds to the control (unexposed) group for case-control studies
No liver metastasis (NLM)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Liver metastasis (LM)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Colorectal patients with liver metastasis (LM) in the supplementary discovery cohort (cohort 1)
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
8
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Within 3 months prior to specimen collection.

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
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
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
4.0

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
increased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-3

Curated date: 2024/04/20

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 4a, 4b and Figure 5c

Description: Taxonomic tree, histogram and heatmap (fig 5) displaying differentially abundant taxa in the cladogram in cohort 1.

Abundance in Group 1: increased abundance in Liver metastasis (LM)

NCBI Quality ControlLinks
Acidobacteriota
Actinomycetota
Armatimonadota
Bacillota
Betaproteobacteria
Burkholderiales
Candidatus Saccharibacteria
Chloroflexia
Cupriavidus
Cyanobacteriota
Deinococci
Deinococcota
Fusobacteriota
Gemmatimonadia
Mycoplasmatota
Nitrospirota
Oxalobacteraceae
Planctomycetota
Spirochaetales
Synergistota
Thermaceae
Thermales
Thermus
Verrucomicrobiota
Bacteroidota

Revision editor(s): Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-3

Curated date: 2024/04/20

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 4a, 4b and Figure 5c

Description: Taxonomic tree, histogram and heatmap (fig 5) displaying differentially abundant taxa in the cladogram in cohort 1.

Abundance in Group 1: decreased abundance in Liver metastasis (LM)

NCBI Quality ControlLinks
Acinetobacter
Alphaproteobacteria
Elusimicrobia
Gammaproteobacteria
Moraxellaceae
Parcubacteria group
Pseudomonadales
Pseudomonadota
Sphingomonadaceae
Sphingomonadales
Sphingomonas

Revision editor(s): Aleru Divine

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-6-3

Curated date: 2024/04/19

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Colorectal patients with liver metastasis (LM) in the discovery cohort (cohort 2)
Group 0 sample size Number of subjects in the control (unexposed) group
36
Group 1 sample size Number of subjects in the case (exposed) group
18

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-3

Curated date: 2024/04/20

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 4c, 4d and Figure 5d

Description: Taxonomic tree, histogram and heatmap (fig 5) displaying differentially abundant taxa in the cladogram in cohort 2.

Abundance in Group 1: increased abundance in Liver metastasis (LM)

NCBI Quality ControlLinks
Alistipes
Bacillota
Bacteroidia
Candidatus Saccharibacteria
Chlorobiota
Chloroflexia
Cyanobacteriota
Fusobacteriota
Gemmatimonadia
Lentisphaerota
Parcubacteria group
Planctomycetota
Prevotella
Prevotellaceae
Rikenellaceae
Spirochaetota
Synergistota
Veillonellaceae
Verrucomicrobiota

Revision editor(s): Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-3

Curated date: 2024/04/20

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 4c, 4d and Figure 5d

Description: Taxonomic tree, histogram and heatmap (fig 5) displaying differentially abundant taxa in the cladogram in cohort 2.

Abundance in Group 1: decreased abundance in Liver metastasis (LM)

NCBI Quality ControlLinks
Acidobacteriota
Actinomycetota
Deinococcota
Mycoplasmatota
Nitrospirota
Porphyromonas
Pseudomonadota

Revision editor(s): Aleru Divine

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-6-3

Curated date: 2024/04/19

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Colorectal patients with liver metastasis (LM) in the validation cohort (cohort 3)
Group 0 sample size Number of subjects in the control (unexposed) group
41
Group 1 sample size Number of subjects in the case (exposed) group
13

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
unchanged
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-3

Curated date: 2024/04/21

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 4e, 4f and Figure 5e

Description: Taxonomic tree, histogram and heatmap (fig 5) displaying differentially abundant taxa in the cladogram in cohort 3.

Abundance in Group 1: increased abundance in Liver metastasis (LM)

NCBI Quality ControlLinks
Alistipes
Anaerostipes
Bacillota
Bulleidia
Chlorobiota
Chloroflexota
Christensenellaceae
Collinsella
Coprococcus
Coxiellaceae
Cyanophyceae
Deltaproteobacteria
Desulfovibrio
Dethiosulfovibrionaceae
Devosia
Dorea
Elusimicrobia
Elusimicrobiaceae
Elusimicrobiales
Elusimicrobiota
Fluviicola
Fusobacteriaceae
Fusobacteriales
Fusobacteriia
Fusobacteriota
Fusobacterium
Gemellaceae
Gemmatimonadia
Gemmiger
Hydrogenophaga
Isosphaeraceae
Lachnobacterium
Lentisphaerota
Methylophilaceae
Muribaculaceae
Nitrosomonadales
Oscillospira
Paraprevotella
Parcubacteria group
Parvimonas
Peptostreptococcus
Phascolarctobacterium
Planctomycetota
Prevotella
Prevotellaceae
Promicromonospora
Pseudoxanthomonas
Pyramidobacter
Rhodomicrobium
Rikenellaceae
Ruminococcus
Spirochaetota
Subdoligranulum
Synechococcaceae
Synechococcales
Synechococcus
Synergistales
Synergistia
Synergistota
Thiotrichales
Tissierellaceae
Veillonellaceae
ABY1ABY1
JG30-KF-CM45JG30-KF-CM45
Bacteroidota

Revision editor(s): Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-6-3

Curated date: 2024/04/21

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 4e, 4f and Figure 5e

Description: Taxonomic tree, histogram and heatmap (fig 5) displaying differentially abundant taxa in the cladogram in cohort 3.

Abundance in Group 1: decreased abundance in Liver metastasis (LM)

NCBI Quality ControlLinks
Odoribacteraceae
Porphyromonas
Verrucomicrobiota
Candidatus Saccharibacteria
Mycoplasmatota
Nitrospirota
Actinomycetota
Deinococcota
Pseudomonadota
Cyanobacteriota
Acidobacteriota

Revision editor(s): Aleru Divine