Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study

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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Jeong S, Liao YT, Tsai MH, Wang YK, Wu IC, Liu CJ, Wu MS, Chan TS, Chen MY, Hu PJ, Kao WY, Liu HC, Tsai MJ, Liu CY, Chang CC, Wu DC, Hsu YH
Journal
BMC microbiology
Year
2024
Keywords:
Bacteroides_caccae, Bifidobacterium_longum, Fusobacteria, GLCMANNANAUT-PWY, Lachnospiraceae_bacterium_5_1_63FAA, Streptococcus_anginosus
BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Experiment 1


Needs review

Curated date: 2024/07/17

Curator: Shulamite

Revision editor(s): Shulamite, Aleru Divine

Subjects

Location of subjects
Taiwan
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
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Chronic gastritis , Gastric cancer CG - Chronic gastritis,chronic gastritis,chronic gastritis (disease),Chronic gastritis (disorder),Chronic gastritis NOS,Chronic gastritis NOS (disorder),Chronic gastritis, NOS,Erosive Gastritis,Erosive gastropathy (disorder),gastritis,gastritis (disease), chronic,Gastritis (disorder),Gastritis [Ambiguous],GASTRITIS HEMORRHAGIC,Gastritis unspecified (disorder),Hemorrhagic Gastritis,Idiopathic erosive/hemorrhagic gastritis (disorder),Other specified gastritis,Other specified gastritis (disorder),Other specified gastritis NOS (disorder),Other specified gastritis, without mention of hemorrhage,Chronic gastritis,Ca body - stomach,ca greater curvature of stomach,Ca lesser curvature - stomach,cancer of stomach,gastric cancer,gastric cancer, intestinal,gastric neoplasm,malignant gastric neoplasm,malignant gastric tumor,malignant neoplasm of body of stomach,malignant neoplasm of lesser curve of stomach,malignant neoplasm of stomach,malignant neoplasm of the stomach,malignant stomach neoplasm,malignant tumor of body of stomach,malignant tumor of greater curve of stomach,malignant tumor of lesser curve of stomach,malignant tumor of stomach,malignant tumor of the stomach,stomach cancer,Gastric cancer
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Chronic gastritis
Group 1 name Corresponds to the case (exposed) group for case-control studies
Gastric Cancer
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants diagnosed with early and late stage gastric cancer.
Group 0 sample size Number of subjects in the control (unexposed) group
33
Group 1 sample size Number of subjects in the case (exposed) group
32
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
6 months

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
Mann-Whitney (Wilcoxon)
edgeR
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
4.27
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/07/21

Curator: Shulamite

Revision editor(s): Shulamite, Aleru Divine

Source: Table 1, 2, 3, Figure 2(a) and 5

Description: Comparative analysis of differential abundance between chronic gastritis and gastric cancer at the phylum, genus, and species levels using the Wilcoxon Rank-Sum Test, EdgeR, and LEfSe.

Abundance in Group 1: increased abundance in Gastric Cancer

NCBI Quality ControlLinks
Bacteroides caccae
Bifidobacterium dentium
Coprococcus
Coprococcus catus
Fusobacteriota
Fusobacterium
Haemophilus
Lactobacillus
Limosilactobacillus fermentum
Limosilactobacillus mucosae
Oscillibacter
Parabacteroides
Parabacteroides distasonis
Phascolarctobacterium
Streptococcus anginosus
Sutterella
Veillonella
unclassified Oscillibacter
unclassified Sutterellaceae

Revision editor(s): Shulamite, Aleru Divine

Signature 2

Needs review

Curated date: 2024/07/21

Curator: Shulamite

Revision editor(s): Shulamite, Aleru Divine

Source: Table 1, 2, 3, Figure 2(a) and 5

Description: Comparative analysis of differential abundance between chronic gastritis and gastric cancer at the phylum, genus, and species levels using the Wilcoxon Rank-Sum Test, EdgeR, and LEfSe.

Abundance in Group 1: decreased abundance in Gastric Cancer

NCBI Quality ControlLinks
Acinetobacter
Actinomycetota
Adlercreutzia
Bifidobacterium
Bifidobacterium longum
Collinsella
Enterococcus
Enterococcus faecium
Eubacterium
Lachnospiraceae bacterium
Morganella
Pseudomonas

Revision editor(s): Shulamite, Aleru Divine

Experiment 2


Needs review

Curated date: 2024/07/21

Curator: Shulamite

Revision editor(s): Shulamite, Aleru Divine

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Other sub-groups (NIM, IM and late-stage gastric cancer))
Group 1 name Corresponds to the case (exposed) group for case-control studies
Early-stage gastric cancer
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants diagnosed with early-stage gastric cancer (Phase I and II).
Group 0 sample size Number of subjects in the control (unexposed) group
52
Group 1 sample size Number of subjects in the case (exposed) group
13

Lab analysis

Statistical Analysis

Statistical test
LEfSe
edgeR

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/10/01

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Table 2, Figure 2(b) and 6

Description: Comparative analysis of differential abundance between chronic gastritis sub-groups and gastric cancer sub-groups using EdgeR, and LEfSe.

Abundance in Group 1: increased abundance in Early-stage gastric cancer

NCBI Quality ControlLinks
Enterococcus
Odoribacter
Phascolarctobacterium
Veillonella
unclassified Sutterellaceae

Revision editor(s): Aleru Divine

Experiment 3


Needs review

Curated date: 2024/10/01

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Other sub-groups (NIM, IM and early-stage gastric cancer)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Late-stage gastric cancer
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants diagnosed with late-stage gastric cancer (Phase III and IV).
Group 0 sample size Number of subjects in the control (unexposed) group
46
Group 1 sample size Number of subjects in the case (exposed) group
19

Lab analysis

Statistical Analysis

Statistical test
edgeR
LEfSe

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/10/01

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Table 2, Figure 2(b) and 6

Description: Comparative analysis of differential abundance between chronic gastritis sub-groups and gastric cancer sub-groups using EdgeR, and LEfSe.

Abundance in Group 1: increased abundance in Late-stage gastric cancer

NCBI Quality ControlLinks
Parabacteroides
Oscillibacter
Fusobacterium
Sutterella

Revision editor(s): Aleru Divine

Experiment 4


Needs review

Curated date: 2024/10/01

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Other sub-groups (NIM, early-stage gastric cancer and late-stage gastric cancer))
Group 1 name Corresponds to the case (exposed) group for case-control studies
Intestinal metaplasia
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants diagnosed with chronic gastritis with pre-cancer lesions (intestinal metaplasia, IM)
Group 0 sample size Number of subjects in the control (unexposed) group
50
Group 1 sample size Number of subjects in the case (exposed) group
15

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/10/01

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Table 2, Figure 2(b) and 6

Description: Comparative analysis of differential abundance between chronic gastritis sub-groups and gastric cancer sub-groups using EdgeR, and LEfSe.

Abundance in Group 1: increased abundance in Intestinal metaplasia

NCBI Quality ControlLinks
Adlercreutzia
Agathobacter rectalis
Anaerostipes
Eubacterium

Revision editor(s): Aleru Divine

Experiment 5


Needs review

Curated date: 2024/10/01

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Other sub-groups (IM, early-stage gastric cancer and late-stage gastric cancer))
Group 1 name Corresponds to the case (exposed) group for case-control studies
Non-intestinal metaplasia
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants diagnosed with chronic gastritis without pre-cancer lesions (non-intestinal metaplasia, IM)
Group 0 sample size Number of subjects in the control (unexposed) group
47
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

Signature 1

Needs review

Curated date: 2024/10/01

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Table 2, Figure 2(b) and 6

Description: Comparative analysis of differential abundance between chronic gastritis sub-groups and gastric cancer sub-groups using EdgeR, and LEfSe.

Abundance in Group 1: increased abundance in Non-intestinal metaplasia

NCBI Quality ControlLinks
Acinetobacter
Megamonas
Pseudomonas

Revision editor(s): Aleru Divine